TW538049B

TW538049B - A novel human osteoclastogenesis inhibitory factor and a process for preparing the same

Info

Publication number: TW538049B
Application number: TW085108022A
Authority: TW
Inventors: Shin Ichi Mochizuki; Tomonori Morinaga; Kazuki Yano; Masaaki Goto; Kanji Higashio
Original assignee: Snow Brand Milk Products Co Ltd
Priority date: 1995-02-20
Filing date: 1996-07-03
Publication date: 2003-06-21
Also published as: ATE391178T1; WO1996026217A1; JP3502102B2; KR100381788B1; DE69637486D1; US7205397B2; EP0816380B1; HU224570B1; US7468268B2; RU2194714C2; KR19980702369A; AU702557B2; AU4677396A; IL117175A; NO973801D0; US20050014229A1; NO973801L; US20050124054A1; EP1528103B1; ATE274580T1

Abstract

A protein which inhibits osteoclast differentiation and/or maturation and a method of production of the protein. The protein is produced by human embryonic lung fibroblasts and has molecular weight of about 60 kD and about 120 kD under non-reducing conditions and about 60 kD under reducing conditions on SDS-polyacrylamide gel electrophoresis, respectively. The protein can be isolated and purified from culture medium of the said fibroblasts. Furthermore, the protein can be produced by gene engineering. The present invention includes cDNA for producing the protein by gene engineering, antibodies having specific affinity to the protein or a method for determination of the protein concentration using the antibodies.

Description

538049 A7 B7 _ 五、發明説明（3 ) 抟術領诚本發明乃對破骨細胞之分化和/或成熟顯示抑制活性的新穎蛋白質，即破骨細胞形成抑制因子（ Osteoclastogenesis Inhibitory Factor,簡稱為0CIF) 和其製造方法有關者。習知桔術經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) 人體的骨質不斷進行吸收和再形成作用。上述作用過程中擔任主要功能的細胞有擔當骨質形成的成骨母細胞和擔當吸收骨質的破骨細胞。上述細胞所扮演功能中，由其代謝異常而造成的典型疾病有骨質疏鬆症。上述疾病乃是由於破骨細胞所造成的骨質吸收超過成骨母細胞所進行的骨質形成而造成的。雖然發生該病的機制尚未完全解明。但該病會引起骨骼之疼痛，骨質之脆化而易造成骨折之原因。隨著高齡人口之增加，這種造成骨折使老人無法離開病床的上述疾病已成為社會問題，所以其治療藥劑之開發研究成為刻不容緩的急務。這種骨質代謝異常所造成的骨量減少症，藉由抑制骨質吸收，促進骨質形成，或改善其代謝平衡等可期待其治療效果。骨骼形成可藉由促進擔任骨骼形成的細胞之增殖，分化和活化，或藉由抑制擔當骨質吸收之細胞的增殖，分化和活化而期待其形成效果。近年來，這種具有上述活性的生理活性蛋白質引起重視而積極展開研究。促進成骨母細胞的增殖或分化的胞質分裂素，已有纖維織母細胞成長因子（Fibroblast growth factor.簡稱為 FGF;參考 Rodan 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 3 3 8 0 7 6 538049 A7 B7_ 五、發明説明（4 ) δ·Β·等人.Endocrinology, 121 卷，1917頁，1987年），類胰島素成長因子- I(Insulir) like growth bactor-I; 簡稱為 IGF-I;參考 Hock J.M♦等人·，Endocrinology, 122卷，254頁，1988年），類胰島素成長因子- II(538049 A7 B7 _ V. Description of the invention (3) Ji Shu Ling Cheng The present invention is a novel protein that shows inhibitory activity on osteoclast differentiation and / or maturation, that is, Osteoclastogenesis Inhibitory Factor (referred to as 0CIF ) Related to its manufacturing method. Learned by Jushu Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling out this page) The bones of the human body continue to absorb and reform. The cells that perform the main functions during the above-mentioned action include osteoblasts that are responsible for bone formation and osteoclasts that are responsible for absorbing bone. Among the functions of these cells, osteoporosis is a typical disease caused by abnormal metabolism. These diseases are caused by bone resorption caused by osteoclasts over bone formation by osteoblasts. Although the mechanism of the disease has not been fully elucidated. However, the disease causes pain in the bones and the brittleness of the bones can easily cause fractures. With the increase of the elderly population, the above-mentioned diseases that cause fractures to prevent the elderly from leaving the hospital bed have become social problems, so the research and development of therapeutic agents has become an urgent task. This type of bone mass reduction caused by abnormal bone metabolism can be expected to have a therapeutic effect by inhibiting bone resorption, promoting bone formation, or improving its metabolic balance. Bone formation can be expected by promoting the proliferation, differentiation, and activation of bone-forming cells, or by inhibiting the proliferation, differentiation, and activation of cells responsible for bone resorption. In recent years, such a physiologically active protein having the above-mentioned activity has attracted attention and has been actively researched. The cytokinin that promotes the proliferation or differentiation of osteoblasts already has Fibroblast growth factor (FGF for short; refer to Rodan) This paper applies Chinese National Standard (CNS) A4 (210X297 mm) ) 3 3 8 0 7 6 538049 A7 B7_ V. Description of the invention (4) δ · Β · et al. Endocrinology, Vol. 121, p. 1917, 1987), Insulir like growth bactor-I ; IGF-I for short; see Hock JM, et al., Endocrinology, Vol. 122, p. 254, 1988), Insulin-like Growth Factor-II (

Inuslin like growth factor-II;簡稱為 IGF- II，參考 Endocrin〇i〇gy, 124 卷，30 1頁，1989 年）苯丙酸諾龍 A( Activin A;參考 Centrella Μ·等人.，Mol.Cell Biol.ll 卷，250頁，1991年），轉化成長因子-/9 (Transforming s〇 w t h f a c t 〇 r -/3 ,參考 N 〇 d a Μ · , T h e Β ο n e , 2 卷，2 9 頁，1988年），脈管托品（Vasculotropin參考 Varonigue Μ· 等人，Biochem, Biophys, Res. Cofflrnun, 199 卷，380 頁， 1994年），以及骨骼形態發生蛋白質（Bone morphogenetic Pr〇tein;簡稱 BMP:BMP-2;參考 Yamaguchi Α·等人· J · C e 1 1 Β i ο ] · C h e m， 1 1 3 卷，6 8 2 頁，1 9 9 1 年，0 Ρ - 1 ;參考 Sampath Τ·Κ♦等人.，J. Biol Cheai. 267 卷，20532 頁，1992年，Knutsen R·等人 *， Biochem· Biophys· Res· Commun· 194 卷，1352 頁，1993 年）等報告。經濟部中央榡準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) 另一方面，有關破骨細胞形成，即抑制破骨細胞之分化和/或成熟的胞質分裂素，已有轉化成長因子-泠（ Transforming growth factor-yS,參考 Chenu C·等人.， Pr· Mat1 · Acad · Sci · US A , 85卷，5 6 8 3 頁，1 9 88 年）或間白素-4(Interleukin-4;參考 Kasano Κ·等人♦， B〇ne~Miner. ,21卷，179頁，1993年）等報告。另外，藉破骨細胞抑制骨質吸收的細質分裂素有降血鈣素（本紙張尺度適用中國國家標準（CNS ) Α4規格（210Χ297公釐） 4 3 8 0 7 6 538049 A7 經濟部中央標準局員工消費合作社印製 B7五、發明説明（5 ) Calcitonin; Bone-Mine「.，17卷，347頁，1992年）巨噬細胞群落剌激因子（Macrophage colony-stimu-lating factor;參考 Hattersley G.等人.，J.Cell Physiol.137卷 ,199頁，1988年），間白素-4(參考Wat anabe K.等人.， Biochem. B i o p h y s . Res. C o m ni u n . 172# , 1035H, 1990年）以及干擾素-7 (Interferon - γ ;參考 Gowen M·等人，，J· Bone Miner. Res., 1 卷，469頁，1986年）等報告出現。上述胞質分裂素可期待其經藉助促進骨質形成或抑制骨質吸收等作用而成為骨量減少症的改善劑。對於上述之部分胞質分裂素，例如類胰島素成長因2-1或骨骼形態發生蛋白質等已做為骨質代謝改善劑在進行臨床試驗。另外 ,降血鈣素已做為骨質疏鬆症之治療藥劑或減輕疼痛藥劑而有市販品。目前，有關骨質疾病的治療以及縮短治療期間為目的之醫藥品，在臨床方面已使用的種類有活化型維生素D3，降血鈣素以及其衍生物，雌二醇等荷爾蒙製劑，7 -異丙氧基異黃酮 IprifleavoneW-Isopropoxyisoflavavane)，維生素K.2(Menatetrenone)或鈴製劑等。然而使用這些藥劑的治療方法和其效率以及其治療結果不一定能令人滿意，仍然希望有更好的治療藥劑開發問市。如前述骨質代謝偽藉骨質形成和骨質吸收之均衡而調節，因此，抑制破骨細胞之分化♦成熟的胞質分裂素，可期待其成為骨質疏鬆症等骨量減少症的治療藥劑。 (請先閱讀背面之注意事項再填寫本頁) 本紙張尺度適用中國國家標準（CNS ) A4規格（210 X 297公釐） 5 3 8 0 7 6 538049 A7 B7 經濟部中央標準局員工消費合作社印製五、發明説明（6 ) 本發明乃據上述觀點，以提供新穎的破骨細胞形成抑制因子（OCIF)和其有效率的製造方法為目的者。本發明研究者有鑑於現況，經多方努力研究結果，在人類胎兒肺纖維織母細胞IMR-90 (ATCC寄存號碼CCL1 86)的培養液中，發現具有破骨細胞形成抑制活性，也就是具有破骨細胞之分化•成熟的抑制活性的蛋白質-0 C I F而完成本發明。另外，也發現以氧化鋁陶瓷Η做為培養細胞時之載體 ,可以在培養基中高濃度的蓄積本發明的破骨細胞形成抑制因子之OCIF,且能提升精製效率。本發明研究者更進一步將前述培養液利用離子交換分離管，親和性分離管以及逆相分離管依序處理而重複進行吸附和溶出操作，確立前述蛋白質0 C I F的高效率精製方法〇其次，本發明研究者根據所得天然型蛋白質OCIF的胺基酸序列資訊，完成該蛋白質的編碼cDN Α的純条增殖。本發明研究者更進而利用該c D N A藉遣傳基因工程方法，確立生産具有破骨細胞之分化和/或成熟之抑制活性的蛋白質的方法。本發明乃有關一種新穎蛋白質者，該蛋白質源自人類胎兒肺纖維織母細胞，在還原條件下，於S D S - P A G E的分子量示約6 0 k D ,在非還原條件下，於S D S - P A G E的分子量示約 6 0 k D以及約1 2 0 k D ,對於陽離子交換物和肝素分離管具有親和性，經由7 0 10下處理1 0分鐘或5 6 °C下處理3 0分鐘的加 (請先閲讀背面之注意事項再填寫本頁) 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 6 3 8 0 7 6 538049 A7 B7 經濟部中央標準局員工消費合作社印製五、發明説明（7 ) 熱處理。其破骨細胞之分化•成熟的抑制活性會降低，經由90 °C下10分鐘的加熱處理，其破骨細胞之分化♦成熟的抑制活性會消失等為其特徵。本發明的蛋白質0CIF的胺基酸序列和已知的破骨細胞形成抑制因子有明確地差異。又，本發明也有關於蛋白質0CIF的製造方法者。該方法乃培養人類纖維織母細胞，利用肝素分離管處理培養液 ,溶出其吸附部分，再利用陽離子交換分離管吸附、溶出 ,再藉親和性分離管，逆相分離管精製而製得前述蛋白質為其特徵。本發明中有關之分離管處理，不僅指將培養液等注入肝素瓊脂糖分離管等處理，也包括利用分批法，將培養液和肝素瓊脂糖等混合而擁有分離管處理同等效率之方法。本發明中所使用親和性分離管，例如肝素分離管以及藍色素分離管。上述藍色素分離管以採用西巴克隆籃色素分離管為最佳。上述西巴古隆籃色素分離管的填充劑以親水性合成高分子化合物為載劑結合以西巴克隆籃色素 F3GA為例舉，通常簡稱為藍色素分離管。本發明也有關使用氣化鋁陶瓷片為載體，進行細胞培養而高效率地製造前述蛋白質之方法者。本發明的蛋白質0 C I F可自人類纖維織母細胞培養液中高效率且高收率地加以分離精製而得。從原料分離精製本發明蛋白質0 C I F之方法，可以按照一般從生物試料中精製蛋白質之常用方法，利用目的物質的蛋白質0CIF的物理、化學特性，藉各種精製操作而進行之。其濃縮方法之例舉有超濾、凍結乾燥、塩析法等一般生化學上常用處理方法 (請先閲讀背面之注意事項再填寫本頁) 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 7 3 8 07 6 538049 A7 B7 經濟部中央標準局員工消費合作社印製五、發明説明（8 ) 。其精製方法之例舉有離子交換色譜法、親和性色譜法、膠濾色譜法、疏水性色譜法、逆相色譜法、調製用電泳法等一般精製蛋白質常用方法加以適當調配組合而採用。其中最佳例舉為原料的人類纖維織母細胞採用人類胎兒肺纖維織母細胞IMR-90UTCC-CCL186)。該原料的人類胎兒肺纖維織母細胞I M R - 9 0的培養，以利用氧化鋁陶瓷片吸附人類胎兒肺纖維織母細胞I M R - 9 0後，使用添加有5 %胎牛血清的DMEM培養基為培養液，在旋轉容器中靜置培養1星期至10日左右而得者為適宜。又進行精製處理時，添加0.1 % C H A P S ( 3 - [( 3 -膽醯胺丙基）-二甲基胺基]-卜丙基磺醯塩 )為界面活化劑後精製為宜。本發明的蛋白質0 C I F ,像藉首先將培養液注入肝素分離管（肝素-壤脂糖CL-6B Pharmacia製品）再用含有2M氣化鈉的1 0 in Μ T r i s -塩酸緩衝液（p Η 7 . 5 )溶出，分離得肝素吸附性的0 C I F部分，再利用Q陰離子交換分離管（H i L 〇 a d -Q/FF, Pharmacia公司製品）處理，收集其非吸附部分而獲得具有肝素吸附性而鹼性的0 C I F部分。所得0 C I F活性部分再經由S ·陽離子交換分離管（Hi Load-S/HP, Pharmacia! 司製品），肝素分離管（肝素-5PW, Tosoh公司製品），西巴克隆籃色素分離管（藍色素- 5PW, Toso公司製品），逆相分離管（Βϋ-300 C4, Perk in-Elmer公司製品）等分離精製而製成，所得本發明物質具備上述特性。本發明依據上述所製得天然型的〇 C I F蛋白質的胺基酸序列，將該蛋白質的編碼c D N A加以純条增殖，再利用該 (請先閱讀背面之注意事項再填寫本頁) 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 8 3 8 0 7 6 538049 A7 B7 五、發明説明（9 ) eDNA藉遣傳基因工程方法製造具有破骨細胞之分化和/或成熟之抑制活性的蛋白質OCIF。因此，本發明也包括上述 _造方法在内。換言之，依照本發明方法所精製的〇 C I F蛋白質，利用内蛋白酶（例如賴胺醯内胜肽酶）處理後，決定所産生胜肽的胺基酸序列，再製造可編碼所得内部胺基酸序列的寡核 #酸的混合物。繼之，以所製得寡核¥酸混合物做為引物（P「i m e r )，利用PCR法（最好採用RT-PCR法）製OCIFcDNA片段。以該 OCIFcDNA片段為探針，從cDNA庫中純条增殖而得0CIF的全部cDNA。所得 OCIFcDNA插人表現載體（Expression vector )而製得0CIF表現質粒（Express丨on plasm丨d),再將之導入各種細胞或菌體中而使之表現，可製得重組型〇 C I F。本發明也包括具有上述活性的本發明蛋白質0CIF之類緣物（Variant)的新穎蛋白質的0CIF2，0CIF3, 0CIF4和 0CIF5。經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) 上述類緣物可藉使用I M R - 9 0細胞的聚U ) + R N A所製成 cDKA庫，以OCIFcDNA片段為探針，經雜化而製成。將 0CIF類緣物的CDNA插入表現載體，再利用一般宿主顯現該〇 C I F類緣物表現載體，再採用常法精製而製得目的物之類緣蛋白質。又，本發明也包括0 C I F變異物在内。上述變異物乃有可能和OC IF的二倍體的形成有關聯的 C y s殘基以S e r殘基取代，或將缺失變異導入天然型〇 C I F而本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 9 3 8 0 7 6 538049 A7 經濟部中央標準局員工消費合作社印製 B7五、發明説明（10 ) 成者。可利用P C R法或以限制酶切割而在0 C I F c D N A導入缺失變異或取代基。再將該cDNA插入在具有適當的表現催化物的載體，然後轉移在哺乳動物細胞等的真核細胞中，再培養該細胞，由其培養液中藉常法精製而獲得目的之 0 C I F變異物。又，本發明也包括抗0 C I F多株抗體，和利用該多株抗體的0 C I F的測定方法在内。上述抗0 C I F多株抗體，乃以0 C I F為免疫原，藉常見方法而製造之。該時所使用的抗原（免疫原），可採用由IMR-9 0培養液所得天然型0 C I F ,以及使用0 C I F c D N A以徼生物或真核細胞為宿主而生産出來的基因重組型0CIF,或根據 0 C I F的胺基酸序列而設計成的合成肽，或0 C I F加水分解所得局部胜肽。利用上述抗原，必要時再併用免疫佐助劑，使適當的哺乳動物成為免疫性，再利用常法由其血清精製而得抗0 C I F多株抗體。再用同位素或酵素將所得抗0 C I F多株抗體予以標記，以此做為放射免疫分析法（Rad丨〇 immunoassay,簡稱為 RIA)或酵素免疫分析法（Enzymeimmunoassay,簡稱為E1A) 之測定条而利用。利用上述測定条可以簡易的達成血液或腹水等生物試料或細胞培養液等中的〇 C I F濃度測定。又，本發明也包括抗0 C I F單株抗體，以及利用該單株抗體而行0 C I F的測定方法。上述抗0 C I F單株抗體偽以0 C I F為免疫原，藉常法製造之。抗原可使用由I M R - 9 0培養液所得天然型0 C I F ,以及使 10 本紙張尺度適用中國國家標準（CNS ) Α4規格（210Χ 297公釐） 3 8 0 7 6 (請先閱讀背面之注意事項再填寫本頁) 538049 A7 經濟部中央標準局員工消費合作社印製 B7五、發明説明）用該OCIFcDNA以微生物或真核細胞為宿主所生産的基因重組型0 C I F ,或依據0 C I F的胺基酸序列而設計的合成胜肽，或0 C I F的加水分解而得局部的胜肽。使用上述抗原使哺乳動物獲得免疫性，或利用試管法而得免疫性細胞，和哺乳動物的骨髓細胞瘤（M y e 1 〇 m a )等融合而製得融合瘤，再從該融合瘤選擇能生産辨識0CIF的抗體純条增殖条，培養上述而得目的之抗體。製造融合瘤之際，如使用哺乳動物時 ,一般常用鼠類等小型動物。免疫操作係利用生理食塩水等將0 C I F稀釋成為適當濃度的溶液，再將該溶液投與在試驗動物的靜脈或腹腔内，必要時再併用免疫佐助劑投與之。上述投與方法為每隔2-20日投與2〜5次而完成。藉上述操作而獲得免疫性的試驗動物，經解剖摘取脾臟，以脾細胞做為免疫細胞而使用。和免疫細胞進行細胞融合的源於小鼠骨髓細胞瘤（ Myeloma)的例舉，有 P3/X63-Ag8, NS-1. , MPC-11 ,$卩-2/0,?0,?3父63688.653,$194等。又家鼠由來的細胞有如R - 2 1 0等細胞株。生産人類抗體時，可藉試管法將人類Β淋巴球獲得免疫，藉人體骨髓細胞瘤細胞或ΕΒ病毒形質轉化的細胞株為母株而獲得可生産人類抗體之融合瘤。免疫細胞和骨髓細胞瘤細胞株間的融合作用可依據周知方法進行。例如採用Κ 〇 e h 1 e r和M i 1 s t ί η等人的方法（參考 Κ 〇 e h 1 e r , G ·等人，N a t u r e , 2 5 6 卷，4 9 5 - 4 9 7 頁，1 9 7 5 年 ),或電脈衝法等。在培養細胞時所使用培養基（不含F B S ) 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） ι ι 3 8 0 7 6 (請先閱讀背面之注意事項再填寫本頁) 538049 A7 經濟部中央標準局員工消費合作社印製 B7五、發明説明（12 ) 中，按照一般所採用細胞數比率，將免疫細胞和骨髄細胞瘤細胞株加以混合，添加聚乙二醇而進行融合處理，然後在Η AT選擇性培養基中培養而選出融合細胞。選別抗0 C I F抗體生産株，可利用一般撿出抗體所常用方法，例如E L I S A法，溶鐘斑法，奧脫洛尼氏法，凝聚法等而進行。據此選出的融合瘤，可藉一般培養方法進行繼代培養，必要時也可以冷凍保存之。可用常見方法培養融合瘤，或移植在哺乳動物的腹腔内而生産抗體。所得抗體可藉塩析法，膠濾法或親和性色譜法等常見方法精製之。所得抗體對於0 C I F表現特異性反應，因此，可提供 0 C I F的測定或精製用途。使用在0 C I P的測定時。可利用同位素或酵素將抗體加以標記，而後利用在R I A或E I A等測定条統中。特別是從本發明所得的抗體，其辨識抗原部位各異，所以可提供三明治型免疫分析用途之特性。藉使用上述測定条統，很容易測定得血液或腹水等生物體試料或細胞培養液等中的0CIF濃度。 0 C I F活性可依據久米川正好等人之方法（參考蛋白質 ♦核酸•酵素，34卷，999頁，1989年）和高橋等人之方法 (參考 Endo-crinology, 122卷，1373頁，1988年）進行測定。即使用生後大約1 7日的鼠骨髓細胞做為標的細胞，於活化型維生素D 3 (鈣化三醇）共存下，藉酒石酸耐性酸性礎酸酶活性誘導抑制試驗而進行形成破骨細胞之抑制試驗。本發明蛋白質的破骨細胞形成抑制因子的〇C I F ,可提供骨質疏鬆症等骨量減少症，風濕症或變形性關節症等骨 12 本紙張尺度適用中國國家標準（CNS ) A4規格（210 X 297公釐） 3 8 0 7 6 (請先閱讀背面之注意事項再填寫本頁) 538049 A7 B7五、發明説明（13 ) 質代謝異常性疾病，或多發性骨髓瘤等骨質代謝異常疾病之的巨為善改和療台之疾述上立確為或途用物成組藥可明質發白本蛋有之含明，發即本〇〇用途使用與原投抗口用經使非所或上與斷投診口學經疫以免後關劑有製病經子因制抑成形胞細骨破有含為做可劑製的質白蛋之的分成性舌 yvl 效有其為人在與投的全安而物成組藥 ¾ 物成組用射注如例為態形劑製的物〇成用組使藥上醫身述物上和。之等子劑因收制吸抑膚成皮形經胞，細劑骨片破舌之，劑發導本點將，可劑，坐時 , 物物成成組組用用射滴注成製而合混劑體形載赋之之用用使採許所容物上成學組劑用製射和注量般份一效加有添上可學中理其藥，劑舌 %V1 賦機無或機有其及以物生衍素維纖類醣酸基胺如例等子因制抑成形胞細骨破的明發本又〇分成組等物合化劑整〇調劑 Η ί p 加注添種法各方成劑般製形一而賦照等述依劑上可化和尚溶 TF，可 OC要，必其視時劑射注製調而合混劑舌賦劑化定穩劑緩 (請先閲讀背面之注意事項再填寫本頁) 經濟部中央標準局員工消費合作社印製吸 bh TTVs ο 「Ίτ > F 圖 Q 廓 d»輪 oa之 -L分 ♦ 1 Η 成理組處出管溶 0 分時 p Η 3 S 料 d 試明 9 .( 説LO品單 3=:¾ 簡用製之使精式示半圖圖分 1 剖第附第第品 ~ 製49 製分精成 ΐ 組 PW出 -5溶素PW 肝-5 理素處。色圖管 ί 藍離分>|理 W 之 „ Ρ 卜管 5 分，ΐ •成_ 素分 i 組目色出 ί 藍逆容用 } 用所使 ί 使時不 } 示圖 5 圖圖廓輪之形情出溶之時 3 本紙張尺度適用中國國家標準（CNS ) Α4規格（2 ί 0 X 297公釐） 3 8 0 7 6 538049 A7 B7 經濟部中央標準局員工消費合作社印製五、發明説明（14 ) 第4圖示最終産品的精製品在還原條件下和非還原條件下經SDS-PAGE之結果。圖中符號之說明如下：第〗，4攔：分子量標記物第2 , 5欄：尖峰6 第3 , 6欄··尖峰7 第5圖示經還原吡啶基乙基化後，賴胺醯基内蛋白酶處理過的尖峰7的組成分，再利用逆相分離管處理時所溶出組成分之輪廓圖。第6圖示天然型（η)和重組型（r)OCIF在非還原條件下之 SDS-PAGE之結果。另外，（E)示由293/EBNA細胞所生産者， (C )示由C Η 0細胞所生産者。圖中符號之說明如下：第1橱：分子量標記物第2欄··單體型η 0 C I F 第3欄：二體型η 0 C I F 第4攔：單體型r 0 C I F ( Ε ) 第5攔：二體型rOC IF (E) 第6攔：單體型rOC IF (C) 第7欄：二體型rOCIP(C) 第7圖示天然型（η )和重組型（r〇 0 C I F ,在還原條件下的 SDS-PAGE之結果。又，（E)示293/EBNA細胞所生産者，（C) 示CH0細胞所生産者。圖中符號之說明如下： 14 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 3 8 0 7 6 (請先閱讀背面之注意事項再填寫本頁) 538049 A7 B7 經濟部中央標準局員工消費合作社印製五、發明説明（15 ) 第8欄：分子量標記物第9攔··單體型η 0 C I F 第10欄：二體型n〇C IF 第1 1攔：單體型r 0 C I F ( E ) 第12攔：二體型rOCIF(E) 第1 3欄：單體型r 0 C I F ( C ) 第14攔：二體型rOC IF (C) 第8圖示去除N -結合型糖鏈的天然型（n )和重組型（r ) 0CIF,在還原條件下SDS-PAGE之結果。另外，（E)示293/ EBNA細胞所生産者，（C)示CH0細胞所生産者。圖中符號之說明如下：第1 5欄：分子量標記物第1 6攔：單體型η 0 C I F 第1 7欄：二體型η 0 C I F 第1 8攔：單體型r 0 C I F ( Ε ) 第19攔：二體型rOC IF (E) 第2 0攔：單體型r 0 C I F ( C ) 第 2 1 攔··二體型 r 0 C I F ( C ) 第9圖示0 C I F和0 C I F 2的胺基酸序列之比較結果。第1 0圖示0 C I F和0 C I F 3的胺基酸序列之比較結果。第1 1圖示0 C I F和0 C I F 4的胺基酸序列之比較結果。第1 2圖示0 C I F和0 C I F 5的胺基酸序列之比較結果。第1 3圖示使用抗0 C I F多株抗體時之0 C I F的校準曲線。第14圖示使用抗0CIF單株抗體時之0CIF的校準曲線。 15 本紙張尺度適用中國國家標準（CNS ) A4規格（210 X 297公釐） 3 8 0 7 6 I--------·裝-- (請先閲讀背面之注意事項再填寫本頁) 訂 -1¾ 538049 A7 經濟部中央標準局員工消費合作社印製 B7五、發明説明（16 ) 第1 5圖示0 C I F治療骨質疏鬆症之功效。本發明藉實施例詳細説明如下。但是本發明不受實施例範圍之局限不待贅述。 [實施例1 ] 人體纖雒繃a細朐T M R - 9 0摈泰液夕謳餺在棍式瓶（490cm2, ll〇x 117mm, Corning公司製品）中，將人類胎兒肺纖維織母細胞I M R - 9 0 ( A T C Ο C C L 1 8 6 )附著在80g的氧化鋁陶瓷片（氧化鋁為99.5 %,日本東芝陶瓷公司製品）上加以培養。培養時使用6 0個棍式瓶，每一瓶中使用500Inl的含有5%胎牛血清的10InMHEPES緩衝液的 DMEM培養基（吉勿可NRL公司製品），在37°C, 5%的二氧化磺共存下靜置培養7〜10日。培養終後回收培養液，再添加新培養基而由一次培養可得3 0升的I M R - 9 0的培養液。該培養液做為試料1。 [實施例2 ] 破骨細朐形成拙制活件夕測宏方法依據久米川正好氏等人之方法（參考蛋白質♦核酸· 酵素，34卷，999頁，1989年）以及高橋氏等人（參考 Endocrinology, 122卷，1373頁，1988年）之方法，進行本發明之蛋白性破骨細胞形成抑制因子的活性測定。質言之，使用自生後約17日的幼鼠分離而得骨髓細胞，在活化型維生素D 3之共存下，以酒石酸耐性酸性磷酸酶活性之誘導做為指標，進行破骨細胞形成之抑制活性測定試驗。即，以含有2 X 1 0 — 8 Μ的活化型維生素D 3和1 0 %胎牛血清的 16 本紙張尺度適用中國國家標準（CNS ) Α4規格（210X 297公釐） 3 8 07 6 (請先閲讀背面之注意事項再填寫本頁) 538049 A7 B7 經濟部中央標準局員工消費合作社印製五、發明説明（17 ) a - Μ E Μ培養基（吉勿可B R L公司製品）稀釋的試料樣品 1 0 0 /i ]放置於9 6洞的微穴盤中，再將由生後約1 7日的幼鼠所得骨髓細胞3 X 1 0 5個懸濁播種在1 0 0 y 1的含有1 0 %胎牛血清的ex - Μ E Μ培養基中，在5 %的二氧化磺中，3 7 °C及 1 0 0 %的濕度條件下培養一星期，在培養第3日和第5曰，將培養液的1 6 0 /i ]廢棄，再添加含有1 X 1 0 — 8 Μ活化型維生素D 3和1 0 %胎牛血清的α - Μ Ε Μ培養基所稀釋而成的試料樣品160/il。培養7日後用磷酸塩緩衝生理食塩水洗淨，再用乙醇/丙酮（1 : 1 )溶液將細胞在室溫下進行一分鐘固定處理。使用酸性礎酸酶活性測定組劑（A c i d P h 〇 s p h a t a s e， Leucocyte,型錄號碼No.387-A, Sigma公司製品）染色而檢驗破骨細胞形成活性，以酒石酸存在下的酸性磷酸酶活性陽性細胞之減少情形做為0 C I F活性。 [實施例3 ] 0 C I F之精· ί ) 用肝素-瓊脂糖C L - 6 B加以精製將大約901的IMR-90培養液（試料1)用0.22/i πι的濾器（親水性微濾盤，2 0 0 0 c id 2 , M i Π - P 〇 r e公司製品）過濾後，分成三次，以含有0 . 3 Μ氛化銷的1 0 m Μ T r i s -塩酸緩衝液（以下簡稱為T r ί s - H c ])在p Η 7 . 5下平衡化處理過的肝素♦瓊脂糖CL-6B分離管（5x4.1c«i,凝_容量為80ml)處理之。以流速5 0 0 m 1 / h r下，用1 0 m Μ T r丨s - H c ] ( p Η 7 · 5 )洗淨後，再用含有2 Μ氯化鈉的1 0 πι Μ Τ r i s - Η c 1 ( ρ Η 7 · 5 )溶洗而得9 0 0 κι 1 的肝素♦瓊脂糖C L - 6 B吸附部分，所得該部分稱為試料2。 (請先閱讀背面之注意事項再填寫本頁) 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 17 3 8 0 7 6 538049 A7 B7 五、發明説明（1 8 ) i i )用 H i L 〇 a d - Q / F F 精製將肝素♦瓊脂糖吸附部分（試料2 )用1 0 m M T r i s - H c 1 ( pH7.5)透析後，加人CHAPS使成為0·]%濃度，在4°C下放置一夜後，分成二次，使用以含有0*1%CHAPS的50fnM Tris-Hc](pH7.5)平衡過的陰離子交換分離管（HiLoad_ Q/FF， 2.6xi0ero, Pharmacia 公司製品）處理，而得 1 0 0 0 m 1的非吸附部分。所得該部分稱為試料3。 iii)用 HiLoad-S/HP精製經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本買) 將上述所得H i L 〇 a d - Q非吸附部分（試料3 )利用以含有 0·1% CHAPS的50mM Tris-Hcl(pH7.5)平衡過的陽離子父換分離管（HiLoad-S/HP，2.6Xl〇cm, PharmacUc 公司製品）處理之。用含有〇.1%(^/^$的5〇1»^11>丨3-^](9}]7.5)洗淨後，在100分鐘内能使氯化鈉成為1M濃度的直線梯度，以每分鐘8ml的流速進行溶洗，按照每12m】做為一鹽分進行級分。將1〜4 0餾分按照每1 〇餾分整理成為四大鹽分，分別取其1 0 0 //]測定〇 C I F活性。在織分1 1〜3 0處觀察到有 0CIF活性（參照第1圖，圖中+ +示破骨細胞形成有δ0%以上被抑制之活性情形，+示破骨細胞形成有3 0〜8 0 %被抑制之活性情形，-示檢驗不出活性情形）。以比活性局的避分2〗〜30做為試驗4。 ίν)用親和性分離管（肝素- 5PW)精製將1 2 0 id 1的試料4用2 4 0 m】的含有0 · 1 % C H A P S的5 0 m Μ Τ r ί s - Η c 1 ( ρ Η 7 . 5 )稀釋後，再以經含有 0 · 1 % C Η Α Ρ S 的 5 〇 ® Μ Tr is-Hcl (ΡΗ7.5)平衡過的親和性分離管（肝素_5PW, 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 1 8 3 8 0 7 6 538049 A7 B7 經濟部中央標準局員工消費合作社印製五、發明説明（]9 ) 0 . 8 X 7 , 5 c m , T 〇 s 〇 h公司製品）處理之。使用含有0 , 1 % CHPAS的50mM Tris-Hc】(pH7.5)洗淨後，以60分鐘裡使成為2 Μ濃度的直線梯度的氯化鈉溶液，按照流速每分鐘 0 . 5 m 1進行溶洗，並按照每餾分0 . 5 m】進行級分。各餾分取其5 0 u 1測定其0 C I F活性，而獲得大約以0 . 7〜1 . 3 Μ氯化鈉溶液所溶洗出來的0 C I F活性餾分1 0 m 1 ,並以此做為試料5 〇 v) 用親和性分離管（藍色素条-5PW)精製將]0ml的試料5用190ml的含有0.1% CHAPS的50mM T>is-Hcl(pH7.5)稀釋後，再用以含有 0.1% CHAPS 的 50mM Tris-Hcl(pH7.5)平衡過的親和性分離管（籃色素- 5PW, 0.5x 5.0cm, Tosoh公司製品）處理之。再用含有0.1% CHAPS的50mM Tris-Hcl(pH7.5)洗淨後，以60分鐘裡成為 2 Μ濃度的直線梯度的氯化鈉溶液，按照每分鐘0 . 5 m 1的流速溶洗，以每餾分0.5m]進行级分。再取各餾分中的25/il 進行0 C I F活性測定，而得大約以1 . 0〜1 . 6 Μ氯化鈉溶液所溶洗出來的餾分4 9〜7 0顯示0 C I F活性（參照第2圖，圖中 + +示被骨細胞形成有8 0 %以上受到抑制之活性情形，+示破骨細胞形成受到3 0〜8 0 %抑制之活性情形）。 ν i )用逆相分離管精製所得餾分4 9〜5 0 m 1中，加入1 0 w 1的2 5 %三氟乙酸後，再用以含有0 . 1 %三氟乙酸的2 5 %乙腈平衡後的逆相分離管處理（BU- 300, C4、2.1x 220mm, Perkin-Elmer公司製品），以6 0分鐘内成為5 5 %濃度的乙腈直線梯度溶液，按 -----------I— (請先閱讀背面之注意事項再填寫本頁)Inuslin like growth factor-II; referred to as IGF-II for short, refer to Endocriniogy, Vol. 124, p. 31, p. 1989) Activin A; refer to Centrella M. et al., Mol. Cell Biol.ll, vol. 250, 1991), Transforming growth factor- / 9 (Transforming sowthfact 〇r-/ 3, refer to No. oda · M, T he Βο ne, vol. 2, p. 29, 1988), Vasculotropin (see Varonigue M. et al., Biochem, Biophys, Res. Cofflrnun, Vol. 199, p. 380, 1994), and bone morphogenetic proteins (Bone morphogenetic PrOtein; BMP: BMP-2; refer to Yamaguchi A. et al. · J · Ce 1 1 Β i ο] · C hem, vol. 1 1 3, 6 8 2 pages, 1991, 0 pp-1; refer to Sampath Τ · KI et al., J. Biol Cheai. Vol. 267, p. 20532, 1992, Knutsen R. et al. *, Biochem. Biophys. Res. Commun, Vol. 194, p. 1352, 1993) and other reports. Printed by the Consumer Cooperatives of the Central Bureau of Standards, Ministry of Economic Affairs (please read the precautions on the back before filling this page) On the other hand, regarding osteoclast formation, that is, inhibition of osteoclast differentiation and / or mature cytokinin Transforming growth factor-y (Transforming growth factor-yS, refer to Chenu C. et al., Pr · Mat1 · Acad · Sci · US A, Vol. 85, 5 6 8 3, 1989) or Interleukin-4 (Interleukin-4; refer to Kasano K. et al. ♦, Bone ~ Miner., Vol. 21, p. 179, 1993) and other reports. In addition, the mitogen that inhibits bone resorption by osteoclasts is calcitonin (this paper size applies Chinese National Standard (CNS) A4 specifications (210 × 297 mm) 4 3 8 0 7 6 538049 A7 Central Bureau of Standards, Ministry of Economic Affairs B7 printed by employee consumer cooperative. V. Invention Description (5) Calcitonin; Bone-Mine "., Vol. 17, p. 347, 1992. Macrophage colony-stimu-lating factor; see Hattersley G. Et al., J. Cell Physiol. Vol. 137, p. 199, 1988), interleukin-4 (see Wat anabe K. et al., Biochem. Biophys. Res. Com ni un. 172 #, 1035H , 1990) and interferon-7 (Interferon-γ; refer to Gowen M. et al., J. Bone Miner. Res., Vol. 1, p. 469, 1986) and other reports appear. The above cytokinins can be expected It acts as an ameliorator of osteopenia by promoting bone formation or inhibiting bone resorption. Some of the cytokinins, such as insulin-like growth factor 2-1 or bone morphogenesis proteins, have been used as bone metabolism. Improvers are undergoing clinical trials. Calcitonin has been marketed as a therapeutic agent for osteoporosis or a pain-relieving agent. At present, there are activated types for the treatment of osteoporosis and for the purpose of shortening the period of treatment. Vitamin D3, calcitonin and its derivatives, hormonal preparations such as estradiol, 7-isopropoxy isoflavones IprifleavoneW-Isopropoxyisoflavavane), vitamin K.2 (Menatetrenone) or bell preparations, etc. However, the treatment with these agents The method, its efficiency, and its treatment results may not be satisfactory. It is still hoped that better therapeutic agents can be developed and marketed. For example, the aforementioned bone metabolism is pseudo-regulated by the balance of bone formation and bone resorption. Therefore, the inhibition of osteoclasts Differentiation ♦ Mature cytokinin can be expected to become a therapeutic agent for osteoporosis and other osteoporosis. (Please read the precautions on the back before filling out this page.) This paper size applies the Chinese National Standard (CNS) A4 specification. (210 X 297 mm) 5 3 8 0 7 6 538049 A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (6) The present invention aims at providing a novel osteoclast formation inhibitory factor (OCIF) and an efficient manufacturing method thereof in accordance with the above viewpoint. In view of the current situation, the researcher of the present invention has studied the results of various efforts, and found that the culture fluid of human fetal lung fibroblasts IMR-90 (ATCC deposit number CCL1 86) has osteoclast formation inhibitory activity, that is, has Bone cell differentiation and mature inhibitory activity protein-0 CIF complete the present invention. In addition, it has been found that the use of alumina ceramics as a carrier for culturing cells can accumulate OCIF of the osteoclast formation inhibitory factor of the present invention in a high concentration in the culture medium, and can improve purification efficiency. The researcher of the present invention further processed the aforementioned culture solution by using an ion exchange separation tube, an affinity separation tube, and a reverse phase separation tube in order to repeat the adsorption and dissolution operations, and established a high-efficiency purification method of the aforementioned protein 0 CIF. Based on the amino acid sequence information of the obtained natural protein OCIF, the researcher of the invention completed the pure strip proliferation of the protein encoding cDN Α. Researchers of the present invention have further utilized this c D N A borrowed genetic engineering method to establish a method for producing a protein having an osteoclast differentiation and / or maturation inhibitory activity. The present invention relates to a novel protein derived from human fetal lung fibroblasts. The molecular weight of the protein on SDS-PAGE is about 60 k D under reducing conditions. The molecular weight is about 60 k D and about 120 k D. It has affinity for cation exchanger and heparin separation tube. Add 10 minutes at 70 0 or 30 minutes at 5 6 ° C (please (Please read the notes on the back before filling this page) This paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm) 6 3 8 0 7 6 538049 A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs Note (7) Heat treatment. Its osteoclast differentiation and maturation inhibitory activity will decrease. After heating at 90 ° C for 10 minutes, its osteoclast differentiation will mature. Its mature inhibitory activity will disappear. The amino acid sequence of the protein OCIF of the present invention is clearly different from known osteoclast formation inhibitors. The present invention also relates to a method for producing a protein 0CIF. The method is to culture human fibroblasts, use a heparin separation tube to process the culture solution, and dissolve the adsorbed part, and then use a cation exchange separation tube to adsorb and dissolve, and then use affinity separation tube and reverse phase separation tube to refine the protein For its characteristics. The separation tube treatment referred to in the present invention not only refers to the treatment of injecting a culture solution or the like into a heparin agarose separation tube, but also includes a method in which the culture solution and the heparin agarose are mixed by a batch method to have the same efficiency as a separation tube treatment. Affinity separation tubes used in the present invention, such as heparin separation tubes and blue pigment separation tubes. The above blue pigment separation tube is preferably a Siba clone basket color separation tube. The filler of the above-mentioned sibaqulon basket pigment separation tube uses a hydrophilic synthetic polymer compound as a carrier combined with siba clone clone basket pigment F3GA as an example, and is usually simply referred to as a blue pigment separation tube. The present invention also relates to a method for efficiently producing the aforementioned protein by performing cell culture using a vaporized aluminum ceramic sheet as a carrier. The protein 0 C I F of the present invention can be obtained by separating and purifying human fibroblast culture medium with high efficiency and high yield. The method of isolating the protein 0 C I F of the present invention from a raw material can be performed by various purification operations using physical and chemical properties of the protein 0 CIF of the target substance in accordance with a method generally used for purifying proteins from biological samples. Examples of its concentration methods are commonly used biochemical methods such as ultrafiltration, freeze-drying, decantation (please read the precautions on the back before filling this page) This paper size is applicable to China National Standard (CNS) A4 specifications ( 210X297 mm) 7 3 8 07 6 538049 A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs. 5. Description of Invention (8). Examples of such purification methods include ion exchange chromatography, affinity chromatography, gel filtration chromatography, hydrophobic chromatography, reversed phase chromatography, and electrophoresis for general preparation, and other methods for general purification of proteins are suitably formulated and used in combination. Among the best-known human fibroblasts are human fetal lung fibroblasts IMR-90UTCC-CCL186). The raw material of human fetal lung fibroblasts IMR-9 90 was cultured. After the human fetal lung fibroblasts IMR-9 was adsorbed with an alumina ceramic sheet, DMEM medium supplemented with 5% fetal bovine serum was used for culture. It is suitable to obtain the liquid culture in a rotating container for about 1 week to 10 days. In the case of refining, 0.1% C H A P S (3-[(3 -cholamidopropyl) -dimethylamino] -bupropanesulfonium) as an interfacial activator is preferably used for purification. The protein 0 CIF of the present invention, like by first injecting the culture solution into a heparin separation tube (product of heparin-polysaccharose CL-6B Pharmacia), and then using 10 in Μ Tris-osmic acid buffer solution (p Η) containing 2M sodium gasification 7.5) Dissolve and separate the heparin-adsorbing 0 CIF fraction, and then use a Q anion exchange separation tube (H i L Oad-Q / FF, manufactured by Pharmacia) to collect the non-adsorbed fraction to obtain heparin adsorption. Sexual and basic 0 CIF part. The obtained 0 CIF active fraction was then passed through an S · cation exchange separation tube (Hi Load-S / HP, manufactured by Pharmacia!), A heparin separation tube (heparin-5PW, manufactured by Tosoh Corporation), and a siba clone basket pigment separation tube (blue pigment). -5PW, manufactured by Toso Co., Ltd.), reverse phase separation tube (B4-300 C4, manufactured by Perk in-Elmer Co., Ltd.), etc., and manufactured by separation and purification. The substance of the present invention has the above characteristics. According to the amino acid sequence of the natural OCIF protein prepared above, the present invention multiplies the coding DNA of the protein by pure strips, and then uses this (please read the precautions on the back before filling this page) Applicable to China National Standard (CNS) A4 specification (210X297 mm) 8 3 8 0 7 6 538049 A7 B7 V. Description of the invention (9) eDNA uses osteoclast differentiation and / or maturation inhibition Active protein OCIF. Therefore, the present invention includes the manufacturing method described above. In other words, after the oCIF protein purified according to the method of the present invention is treated with an endoprotease (such as lysine and endopeptidase), the amino acid sequence of the generated peptide is determined, and the internal amino acid sequence that can be encoded can be manufactured. A mixture of oligonucleotides. Next, the oligonucleotide mixture was used as a primer (P "imer), and the OCIFcDNA fragment was prepared by PCR (preferably RT-PCR method). The OCIFcDNA fragment was used as a probe and purified from the cDNA library. The entire cDNA of 0CIF was obtained by multiplication of the strips. The obtained OCIF cDNA was inserted into a expression vector (Expression vector) to obtain an 0CIF expression plasmid (Express 丨 on plasm 丨 d), which was then introduced into various cells or bacteria to make it express. Recombinant oCIF is obtained. The present invention also includes the novel proteins 0CIF2, 0CIF3, 0CIF4 and 0CIF5 of the novel proteins of the present invention, such as 0CIF, which have the above-mentioned activity. Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please Read the precautions on the back before filling this page.) The above-mentioned marginal species can be made by using IMR-9 poly U) + RNA cDKA library, using OCIF cDNA fragment as a probe, hybridization to make. The CDNA of the 0CIF-type marginal substance is inserted into the expression vector, and then the general host is used to display the 0CIF-type marginal substance expression vector, and then purified by conventional methods to obtain a target-like protein such as the target. In addition, the present invention also includes the 0 CIF variant in The above variants may be replaced by Ser residues or Cys residues associated with the formation of the diploid of OC IF, or the deletion variants may be introduced into the natural 〇CIF and this paper applies the Chinese national standard (CNS ) A4 specification (210X297 mm) 9 3 8 0 7 6 538049 A7 Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs B7 V. Invention description (10) The winners can be PCR-based or cut with restriction enzymes at 0 CIF c. Introduce deletion mutations or substituents into the DNA. Then insert the cDNA into a vector with an appropriate expression catalyst, then transfer it to eukaryotic cells such as mammalian cells, and then culture the cells. The purified 0 CIF variant is obtained by purification. The present invention also includes an anti-0 CIF polyclonal antibody and a method for measuring the 0 CIF using the polyclonal antibody. The anti-0 CIF polyclonal antibody is based on 0 CIF. It is an immunogen and is manufactured by common methods. The antigen (immunogen) used at this time can be natural CIF of 0 CIF obtained from IMR-9 0 culture medium, and use of 0 CIF c DNA to make organisms or eukaryotic cells. Recombinant genetically produced 0CIF produced for the host, or synthetic peptides designed based on the amino acid sequence of 0 CIF, or local peptides obtained by hydrolyzing 0 CIF. Using the above-mentioned antigens, if necessary, combined with immune adjuvants, Appropriate mammals become immune, and then purified from their serum using conventional methods to obtain anti-0 CIF polyclonal antibodies. The obtained anti-0 CIF polyclonal antibody is labeled with an isotope or an enzyme, and used as a measurement strip for a radioimmunoassay (Rad 丨 immunoassay (referred to as RIA)) or an enzyme immunoassay (Enzymeimmunoassay (referred to as E1A)). use. The measurement strip can be used to easily measure the concentration of 0 C I F in biological samples such as blood or ascites, or in cell culture fluids. The present invention also includes an anti-OC I F monoclonal antibody and a method for measuring 0 C I F using the monoclonal antibody. The above-mentioned anti-OC I F monoclonal antibody is made by using an ordinary method of 0 C I F as an immunogen. Antigens can use natural CIFs obtained from IMR-9 0 culture solution, and make 10 paper sizes apply the Chinese National Standard (CNS) A4 specification (210 × 297 mm) 3 8 0 7 6 (Please read the precautions on the back first (Fill in this page again) 538049 A7 Printed by the Consumer Cooperatives of the Central Bureau of Standards, Ministry of Economic Affairs, B7 V. Invention Description) Use this OCIFcDNA to produce a recombinant 0 CIF produced by a microorganism or a eukaryotic cell as a host, or an amino group based on 0 CIF Synthetic peptides designed based on acid sequences, or hydrolyzed by 0 CIF to obtain local peptides. The above antigen is used to obtain immunity in mammals, or immune cells are obtained by in vitro method, and fusions with mammalian myeloma (Myeoma) are made to produce fusion tumors, and the fusion tumors can be selected for production. Recognize the pure antibody proliferation strips of 0CIF, and cultivate the above-mentioned antibodies to obtain the desired antibodies. When manufacturing fusion tumors, when using mammals, small animals such as mice are usually used. The immunization operation is to dilute 0 C I F into a solution of appropriate concentration with physiological food water, etc., and then administer the solution to the vein or abdominal cavity of the test animal, and if necessary, it is administered with an immune adjuvant. The above-mentioned administration method is completed 2 to 5 times every 2-20 days. The test animal that obtained immunity by the above operation was dissected to extract the spleen, and the spleen cells were used as immune cells. Examples of mouse bone marrow cell tumor (Myeloma) for cell fusion with immune cells are P3 / X63-Ag8, NS-1., MPC-11, $ 卩 -2/0,? 0,? 3 63688.653, $ 194 and so on. The cells derived from domestic mice are cell lines such as R-2 10. When producing human antibodies, human beta lymphocytes can be immunized by in vitro methods, and human myeloma cells or EB virus-transformed cell lines can be used as the parent strain to obtain human antibody-producing fusion tumors. The fusion between the immune cells and the myeloma cell line can be performed according to a known method. For example, the method of Köeh 1 er and Mi st η et al. (Refer to Köeh 1 er, G. et al., Nature, Vol. 2 5 6, 4 9 5-4 9 7 pages, 1 9 7 5 years), or electrical pulse method. Medium used when culturing cells (excluding FBS) This paper size applies Chinese National Standard (CNS) A4 (210X297 mm) ι ι 3 8 0 7 6 (Please read the precautions on the back before filling this page) 538049 A7 Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs B7 5. In the description of the invention (12), the immune cells and epiphyseal cell tumor cell lines are mixed according to the ratio of cell numbers generally used, and polyethylene glycol is added for fusion treatment Then, the fusion cells were selected by culturing in the AT selective medium. The selection of anti-OCI F antibody producing strains can be carried out by methods commonly used for picking up antibodies, such as the EL ISA method, the bell solution method, the Otloni method, and the agglomeration method. The fusion tumors thus selected can be subcultured by ordinary culture methods, and can also be stored frozen if necessary. Fused tumors can be cultured by common methods or transplanted into the abdominal cavity of mammals to produce antibodies. The obtained antibody can be purified by common methods such as decantation, gel filtration or affinity chromatography. The obtained antibody exhibits a specific response to 0 C I F. Therefore, it can be used for the measurement or purification of 0 C I F. When measuring at 0 C I P. Antibodies can be labeled with isotopes or enzymes and then used in assays such as R I A or E I A. In particular, the antibodies obtained from the present invention have different recognition sites for antigens, and thus can provide characteristics for sandwich-type immunoassay applications. By using the above measurement system, it is easy to measure the 0CIF concentration in a biological sample such as blood or ascites, or a cell culture fluid. 0 CIF activity can be performed according to the method of Kumegawa et al. (Refer to protein ♦ Nucleic Acids and Enzymes, Vol. 34, p. 999, 1989) and the method of Takahashi et al. (See Endo-crinology, Vol. 122, p. 1373, 1988) Determination. In other words, using rat bone marrow cells as the target cells for about 17 days after birth, in the presence of activated vitamin D 3 (calcitriol), the osteoclast formation inhibition test was performed by using the tartrate-resistant acid basic enzyme activity induction inhibition test. . OCIF of the osteoclast formation inhibitory factor of the protein of the present invention can provide bone loss such as osteoporosis, rheumatism or deformable arthritis, etc. 12 This paper size applies to Chinese National Standard (CNS) A4 specification (210 X 297 mm) 3 8 0 7 6 (Please read the precautions on the back before filling out this page) 538049 A7 B7 V. Description of the invention (13) Diseases with abnormal bone mass metabolism, such as multiple myeloma, etc. Juwei's reforms and treatment of the disease states that it is indeed a group of medicines that can be used or used. The ingredients can be whitened and the egg can be clear. The hair is used for the same purpose as the original anti-oral agent. Or you can go to the clinic for oral epidemics to prevent the disease. The meridian has the ability to suppress the formation of osteoblasts and the broken bones. It has a split tongue YVL that can be used as a pharmaceutical protein. It is effective for humans. A group of medicines that are administered in combination with a whole body of medicine ¾ a group of objects for injection, such as a state-form preparation made by injection. A group of medicines makes the medicine and the body to neutralize. The sub-agents are produced by injecting and suppressing the skin into skin-shaped meridians, and the fine particles are used to break the tongue. The agent will be guided at this point. When the agent is sitting, the objects are grouped into groups. The use of the body shape of the mixture makes it possible to make the dose and volume of the medicines on the contents of the medicine. It is added with the medicine that can be learned, and the agent% V1 is not available. There are some biochemical derivatives such as fibrillar glycosyl amines, such as the example, which can inhibit the formation of osteoblasts, and then divide them into groups and other chemical compounds. Adjusting agents p p Adding seeds According to the formulations of all parties in France, the formulations can be made according to the formula, and the monk soluble TF can be used on the agent, but the OC must be adjusted according to the time of injection injection and the mixture of the tongue and the stabilizer should be stabilized (please (Please read the notes on the back before filling in this page) Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs bh TTVs ο "Ίτ > F Figure Q Outline d» Round oa -L points ♦ 1 Η Out of the Department of Management Dissolve 0 minutes p Η 3 S material d test 9 (say LO Item 3 =: ¾ The simplified display is used to make the semi-finished picture. The figure is divided into the first and second parts. The system is divided into 49 parts. Tube ί Blue detachment > | Management W „PB tube 5 points, 成 • Cheng _ prime points i group look out ί Blue inverse use} use what makes til time} Figure 5 Figure contour wheel At the time of dissolution 3 This paper size applies the Chinese National Standard (CNS) A4 specification (2 ί 0 X 297 mm) 3 8 0 7 6 538049 A7 B7 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs Explanation (14) The fourth figure shows the results of SDS-PAGE of the refined product of the final product under reducing conditions and non-reducing conditions. The explanation of the symbols in the figure is as follows: No. 4 and 4: Columns 2 and 5 of molecular weight markers ： Spirit 6 Columns 3, 6 ·· Spirit 7 Figure 5 shows the composition of spike 7 treated with lysyl hydrazone endoprotease after reductive pyridylethylation, and then eluted during reverse phase separation tube treatment The outline of the composition. Figure 6 shows the SDS-PAGE of natural (η) and recombinant (r) OCIF under non-reducing conditions. Fruit. Further, (E) being shown by the producer 293 / EBNA cells, (C) shows the producer cells by a C Η 0. The symbols in the figure are explained as follows: Cabinet 1: Molecular weight markers Column 2 · Haplotype η 0 CIF Column 3: Dimorph η 0 CIF Block 4: Haplotype r 0 CIF (E) Block 5 : Dimorphic rOC IF (E) Block 6: Haplotype rOC IF (C) Column 7: Dimorphic rOCIP (C) Figure 7 shows the natural (η) and recombinant (r0 0 CIF). The results of SDS-PAGE under the conditions. Also, (E) shows the producers of 293 / EBNA cells, and (C) shows the producers of CH0 cells. The explanation of the symbols in the figure is as follows: 14 This paper scale applies the Chinese National Standard (CNS ) A4 size (210X 297 mm) 3 8 0 7 6 (Please read the notes on the back before filling out this page) 538049 A7 B7 Printed by the Staff Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of invention (15) Column 8 : Molecular weight marker 9th column · haplotype η 0 CIF Column 10: dimorphic nocC IF column 1: haplotype r 0 CIF (E) 12th column: dimorphic rOCIF (E) section Column 1: Haplotype r 0 CIF (C) Block 14: Dimorphic rOC IF (C) Figure 8 shows the natural (n) and recombinant (r) 0CIF with N-binding sugar chains removed, in S under reducing conditions Results of DS-PAGE. In addition, (E) shows the producers of 293 / EBNA cells, and (C) shows the producers of CH0 cells. The symbols in the figure are explained as follows: Column 15: Molecular weight marker 16th block: Haplotype η 0 CIF Column 17: Dimorph η 0 CIF Block 18: Haplotype r 0 CIF (E) Block 19: Dimorph rOC IF (E) Block 20: Haplotype r 0 CIF (C) No. 2 1 · Dimorphic r 0 CIF (C) No. 9 shows the comparison of amino acid sequences between 0 CIF and 0 CIF 2. No. 10 shows 0 CIF and 0 CIF 3 Comparison results of amino acid sequences. The first 11 shows the comparison results of the amino acid sequences of 0 CIF and 0 CIF 4. The first 12 shows the comparison results of the amino acid sequences of 0 CIF and 0 CIF 5. Part 1 Figure 3 shows the calibration curve of 0 CIF when anti-0 CIF antibody is used. Figure 14 shows the calibration curve of 0 CIF when anti-0 CIF antibody is used. 15 This paper is in accordance with China National Standard (CNS) A4 specification (210 X 297 mm) 3 8 0 7 6 I -------- · install-(Please read the precautions on the back before filling in this page) Order -1¾ 538049 A7 Consumer Co-operation of Central Standards Bureau, Ministry of Economic Affairs Printed five B7, description of the invention (16) 1 5 0 C I F illustrates the therapeutic efficacy of osteoporosis. The present invention is explained in detail by embodiments as follows. However, the present invention is not limited by the scope of the embodiments and need not be described in detail. [Example 1] Human fibrillary bandage A fine TMR-990 Thai liquid syrup in a stick bottle (490cm2, 110x117mm, manufactured by Corning), human fetal lung fibroblasts IMR- 9 0 (ATC 〇 CCL 1 8 6) was attached to 80 g of alumina ceramic sheet (99.5% alumina, manufactured by Toshiba Ceramics Co., Ltd.) and cultured. For cultivation, 60 stick bottles were used. Each bottle used 500 Inl of DMEM medium containing 10 InMHEPES buffer containing 5% fetal bovine serum (made by Jebel NRL) at 37 ° C, 5% sulfur dioxide. Incubate for 7 to 10 days under coexistence. After the end of the culture, the culture solution was recovered, and a new culture medium was added to obtain 30 liters of IM R-90 culture solution from one culture. This culture solution was used as sample 1. [Example 2] The method of forming a broken piece to create a fake job is based on the method of Kumegawa Koshikawa et al. (Refer to Protein ♦ Nucleic Acids, Enzymes, Vol. 34, p. 999, 1989) and Takahashi et al. (Reference Endocrinology, Vol. 122, p. 1373, 1988) was used to measure the activity of the proteinaceous osteoclast formation inhibitor of the present invention. In other words, bone marrow cells were isolated from young rats about 17 days after birth. In the coexistence of activated vitamin D 3, the induction of tartaric acid-resistant acid phosphatase activity was used as an indicator to inhibit the osteoclast formation. Determination test. That is, 16 paper sizes containing 2 X 1 0-8 M of activated vitamin D 3 and 10% fetal bovine serum are applicable to the Chinese National Standard (CNS) Α4 size (210X 297 mm) 3 8 07 6 (Please (Please read the notes on the back before filling this page) 538049 A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (17) a-Μ E Μ media (products of Jebel BRL) diluted sample 1 0 0 / i] Placed in a 96-well micro-cavity disk, and then bone marrow cells 3 X 1 0 5 from the young rats about 17 days after birth were seeded in a suspension at 10 0 y 1 containing 10% fetuses. The bovine serum was cultured in ex-M E M medium in 5% sulphur dioxide at 37 ° C and 100% humidity for one week. On the 3rd and 5th day of culture, the culture solution was It was discarded, and then a sample of 160 / il diluted with α-M E M medium containing 1 X 1 0-8 M activated vitamin D 3 and 10% fetal bovine serum was added. After 7 days of culture, the cells were washed with phosphate buffered saline and then washed with ethanol / acetone (1: 1) solution to fix the cells for one minute at room temperature. The osteoclast-forming activity was examined by staining with an acid basic enzyme activity assay group (A cid Phosphatase, Leucocyte, Catalog No. 387-A, Sigma), and the acid phosphatase activity in the presence of tartaric acid The decrease in positive cells was taken as 0 CIF activity. [Example 3] 0 CIF Essence ·) Refined with heparin-sepharose CL-6 B. IMR-90 culture solution (sample 1) of about 901 was filtered with a 0.22 / i π filter (hydrophilic microfiltration disc, 2 0 0 0 c id 2, product of M i Π-P ore company) after filtration, divided into three times, with 10 m Tris-acetic acid buffer solution (hereinafter referred to as T r ί s-H c]) was treated at p Η 7.5 after equilibrating the treated heparin ♦ Sepharose CL-6B separation tube (5x4.1c «i, coagulation capacity 80ml). After washing with 10 m Μ T r 丨 s-H c] (p Η 7 · 5) at a flow rate of 500 m 1 / hr, it was then washed with 10 π Μ Τ ris containing 2 mM sodium chloride. -Ηc 1 (ρ Η 7 · 5) was dissolved to obtain 9 0 κι 1 heparin ♦ Sepharose CL-6 B adsorption part, the obtained part is called sample 2. (Please read the precautions on the back before filling this page) This paper size applies Chinese National Standard (CNS) A4 specification (210X 297 mm) 17 3 8 0 7 6 538049 A7 B7 V. Description of invention (1 8) ii) Refined with HiL 〇ad-Q / FF. The heparin agarose adsorption part (sample 2) was dialyzed against 10 m MT ris-H c 1 (pH 7.5), and added CHAPS to a concentration of 0 ·]%. After being left overnight at 4 ° C, it was divided into two parts and an anion exchange separation tube (HiLoad_Q / FF, 2.6xi0ero, Pharmacia) equilibrated with 50fnM Tris-Hc] (pH7.5) containing 0 * 1% CHAPS was used. Company's products) to obtain a non-adsorbed portion of 100 m. The obtained part is called sample 3. iii) Printed by HiLoad-S / HP Refined by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling in this purchase) Use the H i L 〇ad-Q non-adsorbed part (sample 3) obtained above A 50 mM Tris-Hcl (pH 7.5) equilibrated cationic parent exchange separation tube (HiLoad-S / HP, 2.6 × 10 cm, manufactured by PharmacUc) containing 0.1% CHAPS was used for treatment. After washing with 0.1% (^ 0 ^^ 50〇 »^ 11 > 丨 3-^] (9)] 7.5), the linear gradient of sodium chloride to 1M concentration can be achieved within 100 minutes. The solution was washed at a flow rate of 8 ml per minute, and fractions were taken as a salt every 12 m. The 1 to 40 fractions were sorted into four major salts per 10 fractions, and each of them was taken as 1 0 0 //] to measure. CIF activity. 0CIF activity was observed at weaving points 1 1 to 30 (refer to Figure 1, + + shows osteoclast formation is inhibited by δ0% or more, + shows osteoclast formation 3 0 ~ 80% of the inhibited activity,-shows that no activity can be detected). The specific activity of the avoidance points 2 to 30 as the test 4. ίν) using affinity separation tube (heparin-5PW) refined Sample 4 of 1 2 0 id 1 was diluted with 2 4 0 m] of 50 m Μ Τ r s-Η c 1 (ρ Η 7.5) containing 0 · 1% CHAPS, and then was added with 0 · 1% C Η Α Ρ S 50 〇 Μ Tr is-Hcl (P 7.5) balanced affinity separation tube (heparin_5PW, this paper size applies Chinese National Standard (CNS) A4 specifications (210X 297 mm ) 1 8 3 8 0 7 6 538049 A7 B7 Warp Central Bureau of Standards portion printed consumer cooperative five employees, the invention described (] 9) 0. 8 X 7, 5 c m, T h billion billion company s products) of the process. After washing with 50 mM Tris-Hc [0.1% CHPAS] (pH 7.5), a sodium chloride solution with a linear gradient of 2 M concentration was obtained in 60 minutes at a flow rate of 0.5 m 1 per minute. Dissolve and fractionate at 0.5 m per fraction]. Take 50 u 1 of each fraction to measure its 0 CIF activity, and obtain about 0 CIF active fraction 10 m 1 which was washed out with 0.7 ~ 1.3 M sodium chloride solution, and use this as a sample. 5 〇v) Purified with affinity separation tube (blue pigment strip-5PW) 0ml of sample 5 was diluted with 190ml of 50mM T &is; Hcl (pH7.5) containing 0.1% CHAPS, and then used to contain 0.1 % CHAPS 50 mM Tris-Hcl (pH 7.5) equilibrated affinity separation tube (basket pigment-5PW, 0.5x 5.0cm, manufactured by Tosoh) was processed. After washing with 50% Tris-Hcl (pH 7.5) containing 0.1% CHAPS, the solution was washed with a sodium chloride solution with a linear gradient of 2 M concentration in 60 minutes at a flow rate of 0.5 m 1 per minute. Fractions were performed at 0.5 m per fraction. Then, 25 / il of each fraction was taken for 0 CIF activity measurement, and fractions washed out with 1.0 to 1.6 M sodium chloride solution 4 9 to 7 0 showed 0 CIF activity (refer to Section 2). In the figure, + + indicates that the formation of osteoclasts is inhibited by more than 80%, and + indicates that the formation of osteoclasts is inhibited by 30% to 80%. ν i) using a reverse phase separation tube to refine the obtained fraction 4 9 to 50 m 1, add 10 w 1 of 25% trifluoroacetic acid, and then use 25% acetonitrile containing 0.1% trifluoroacetic acid Equilibrated reverse-phase separation tube treatment (BU-300, C4, 2.1x 220mm, manufactured by Perkin-Elmer), it becomes a linear gradient solution of 5% acetonitrile in 60 minutes. Press ------- ---- I— (Please read the notes on the back before filling this page)

、1T -1¾. 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 19 3 8 0 7 6 538049 A7 B7 五、發明説明（2 0 ) 照每分鐘0 . 2 m 1的流速溶洗分取各餾分（參照第3圖）。使用各尖峰餾分中的1 0 0 /i 1進行0 C I F活性測定，在尖峰6和 7的餾分撿驗到濃度依賴性的有0 C I F活性部分，其結果示於表1。表1 由#相分離管溶冼得0 C I F活件部分情形稀釋率 1/40 1/120 1/360 1/1080 尖峰 6 + + + + + - 尖峰 7 + + + _ - — ------------衣-- (請先閱讀背面之注意事項再填寫本頁) 經濟部中央標準局員工消費合作社印製 (上表中，+ +示破骨細胞形成受到8 0 %以上抑制之活性情形，+示破骨細胞形成受到3 0〜8 0 %抑制之活性情形， -示撿驗不出活性）。 [實施例4 ] 0 C I F ^分芊量測宏利用確認有0 C I F活性之織分尖峰6和尖峰7各4 0 /i 1 , 在還原條件下和非還原條件下，以S D S -聚丙烯醯胺凝膠進行電泳分析。即，分別取2 0 w 1的各尖峰餾分放入2支試管中，經減壓濃縮後，用含有1 m Μ E D T A , 2 . 5 % S D S和0 · 0 1 %溴化苯藍的1 0 m Μ T r ί s - H c 1 ( p Η 8 ) 1 . 5 u 1加以溶解，分別在非還原條件下和還原條件下（5 % 2 -巯基乙醇共存下）於 3 7 °C放置一夜後，分別取其1 /i 1進行S D S -聚丙烯_胺凝膠電泳分析。該電泳使用10〜〗5%丙烯醯胺的悌度凝(、 1T -1¾. This paper size is applicable to Chinese National Standard (CNS) A4 specification (210X 297mm) 19 3 8 0 7 6 538049 A7 B7 V. Description of the invention (2 0) According to the flow of 0.2 m 1 per minute Instant fractions were taken from each fraction (see Figure 3). The 0 C I F activity was measured using 100 0 / i 1 in each of the peak fractions. Concentration-dependent 0 C I F active fractions were detected in the peaks 6 and 7 and the results are shown in Table 1. Table 1 0 CIF solution was obtained from #phase separation tube. Dilution rate of some cases 1/40 1/120 1/360 1/1080 Spike 6 + + + + +-Spike 7 + + + _-— ---- -------- Clothing-(Please read the precautions on the back before filling this page) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (+ in the table above, + + indicates that osteoclast formation is affected by 80% The above-mentioned inhibited activity cases, + indicates that the osteoclast formation was inhibited by 30 ~ 80%, and-indicated that no activity could be detected). [Example 4] The 0 CIF 芊 tiller measurement macro uses the weaving peaks 6 and 7 which are confirmed to have 0 CIF activity, each of 4 0 / i 1, under reducing and non-reducing conditions, using SDS-polypropylene 醯The amine gel was subjected to electrophoretic analysis. That is, each spike fraction of 20 w 1 was put into two test tubes, and after concentrated under reduced pressure, 10 mg of bromine benzene blue containing 1 m EDTA, 2.5% SDS, and 0.1% bromide blue was used. m Μ T r ί s-H c 1 (p Η 8) 1.5 u 1 was dissolved, and stored under non-reducing and reducing conditions (5% 2-mercaptoethanol co-existence) at 37 ° C overnight Then, take 1 / i 1 of them respectively for SDS-polypropylene_amine gel electrophoresis analysis. This electrophoresis uses 10 to 5% acrylamide,

、tT d 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 20 3 8 0 7 6 538049 經濟部中央標準局員工消費合作社印製 A 7 B7五、發明説明（2 1 ) Pharmacia公司製品），藉Phast System電泳儀（ P h a r hi a c i a公司製品）進行。分子量標記使用磷酸化酶Μ 9 4 k D ),牛血清白蛋白（6 7 k D ),卵蛋清（4 3 k D ),碩酸酐酶（ 30kD),胰蛋白酶抑制劑（20.0kD), cx-乳白蛋白（14.4kD) 。電泳分析後，以P h a s t凝_銀染組劑（P h a s t g e 1 silver staini kit, Pharmacia公司製品）進行銀染色。其結果示於第4圖。上述結果，在餾分尖峰6處，還原條件下或非還原條件下，大約6 0 k D處撿驗的蛋白質分離帶。另外，餾分尖峰 7在還原條件下，於約6 0 k D ,非還原條件下在約6 0 k D處，非還原條件下，在約1 2 0 k D處確認蛋白質之分離帶。因此，推測餾分尖峰7係尖峰6的蛋白質同質二量體。 [實施例5 ] 0 C I F之熱穩宙件試驗從籃色条-5PW餾分51〜52的混合試料中各取20/i 1, 加入1 0 m Μ的磷酸塩緩衝生理食塩水（p Η 7 . 2 ) 3 0 // 1之後，分別在7 0 °C , 9 0 °C下各進行1 0分鐘的加熱處理，另外在5 6 °C 下進行3 0分鐘的熱處理。再用該試料按照實施例2所記載方法測定0 C I F活性。其結果示於表2中。 (請先閱讀背面之注意事項再填寫本頁)、 TT d This paper size is applicable to Chinese National Standard (CNS) A4 specification (210X297 mm) 20 3 8 0 7 6 538049 Printed by A 7 B7 of the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of invention (2 1) Pharmacia Products), using a Phast System electrophoresis instrument (products of Phar Hiacia). Molecular weight markers use phosphorylase M 9 4 k D), bovine serum albumin (67 k D), egg and egg white (43 k D), maleic anhydrase (30 kD), trypsin inhibitor (20.0 kD), cx -Lactalbumin (14.4kD). After the electrophoresis analysis, silver staining was performed with a Phas a silver staining agent (Phas t g e 1 silver staini kit, manufactured by Pharmacia). The results are shown in Fig. 4. From the above results, a protein separation band of about 60 kD was detected at 6 peaks of the fraction under reducing or non-reducing conditions. In addition, the peak 7 of the fraction was identified at about 60 kD under reducing conditions, at about 60 kD under non-reducing conditions, and at about 120 kD under non-reducing conditions. Therefore, it is speculated that the fraction spike 7 is a protein homoduplex of the spike 6. [Example 5] 0 CIF thermal stability test Take 20 / i from each of the mixed samples of basket color bars-5PW fractions 51 to 52, and add 10 μM phosphate buffered physiological food water (p Η 7 2) After 3 0 // 1, heat treatment was performed at 70 ° C and 90 ° C for 10 minutes, and heat treatment was performed at 5 6 ° C for 30 minutes. Using this sample, the 0 C I F activity was measured according to the method described in Example 2. The results are shown in Table 2. (Please read the notes on the back before filling this page)

、1T 本紙張尺度適用中國國家標準（CNS ) Α4規格（210Χ 297公釐） 3 8 0 7 6 538049 A7 B7五、發明説明（2 2 ) 恙2 0CIF之熱穩亩件稀釋率 1/300 1/900 1/2700 未處理 7 0 1C下1 0分鐘 5 6 °C下3 0分鐘 9 0 °C下1 0分鐘 (請先閱讀背面之注意事項再填寫本頁) 經濟部中央標準局員工消費合作社印製 (上表中，+ +示破骨細胞形成受到85%以上抑制之活性，+示破骨細胞形成受到3 0〜8 0 %抑制之活性，-示無法檢驗出活性）。 [實施例6 ] 肉部胺某酴序列之決宙就藍色条-5 P W餾分5 1〜7 0 ,將每兩個餾分加以混合成為1 ir 1 ,各試料中分別加入1 0 1的2 5 %三氟乙酸後，每 1ml分成10次用以含有0.1 %三氟乙酸的25 %乙腈所平衡過的逆相分離管（BU-300, C4, 2.lx220mro, Perkin-Elmer 公司製品）處理，以60分鐘内成為55 %濃度的乙腈直線梯度溶液溶洗，其流速為每分鐘〇 . 2 m 1 ,而收集尖峰6和尖峰7的餾分。就所得尖峰6和尖峰7餾分的一部分，分別使用蛋白質序列分析儀（專業規格494型，Perkin-Elmer公司製品），分析N末端胺基酸序列分析，由於無法分析，推測該蛋白質的末端很可能被封阻。因此，就該蛋白質進本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 22 3 8 0 7 6 經濟部中央標準局員工消費合作社印製 538049 A7 B7 五、發明説明（2 3 ) 行内部胺基酸序列分析。即，分別將尖峰6和尖峰7餾分行離心濃縮後，分別加入1 0 0 w g二硫蘇糖醇（ Dithiothreitol), lOmM EDTA， 7M塩酸胍，和含有 CHAPS 的 0.5M Tris-Hcl(pH8.5)50/i 1,在室溫下放置 4 小時，經還原後，加入0.2^1的4 -乙烯基吡啶，在室溫暗處放置一夜進行吡啶乙基化作用。該試料1 U 1中加入2 5 %的三氟乙酸，以含有0 , 1 %三氟乙酸的2 0 %乙腈平衡過的逆相分離管（BU-300, C4, 2.1x30mm, Perkin-E]mer公司製品）處理，再用30分鐘内成為50%濃度的乙腈直線梯度溶液，以每分鐘0 . 3 m 1的流速溶洗，而得還原吡啶乙基化的 0 C I F試料。將上述試料分別離心濃縮後，用8 Μ的尿素，以及含 0,1% Tween80 的 0.1Μ Tris-Hcl(pH9)25/i 1 溶解之後，再用 73W1 的 0.1M Tris-Hcl(pH9)稀釋，加入 0.02/ig AP1(_胺醯内蛋白日本和光純藥公司製品），在37°C 下反應1 5分鐘。反應液中加入1 /i 1的2 5 %三氟乙酸，以經 0.1%三氟乙酸平衡過的逆相分離管（RP-300, C8， 2, IX 220mm, Perkin-Elmer公司製品）處理，以70分鐘内成為50 %濃度的乙腈直線梯度溶液，每分鐘0.2ml的流速下溶洗而得肽片段（參照第5圖）。所得肽片段（p丨〜P 3 )利用蛋白質序列分析儀分析其胺基酸序列，其結果示於序列表中序列號碼1〜3。 [實施例7 ] cDNA序列之決宗、 1T This paper size applies the Chinese National Standard (CNS) A4 specification (210 × 297 mm) 3 8 0 7 6 538049 A7 B7 V. Description of the invention (2 2) IF 2 0CIF thermal stability per piece dilution rate 1/300 1 / 900 1/2700 Untreated 7 0 1C 10 minutes 5 6 ° C 30 minutes 9 0 ° C 10 minutes (Please read the precautions on the back before filling this page) Employees of the Central Standards Bureau of the Ministry of Economic Affairs Printed by a cooperative (in the table above, + indicates the activity that inhibits osteoclast formation by more than 85%, + indicates the activity that inhibits osteoclast formation from 30 to 80%, and-indicates that the activity cannot be detected). [Example 6] The decisive sequence of some amines in the meat portion is the blue strip-5 PW fractions 5 1 ~ 7 0. Each two fractions are mixed to become 1 ir 1, and 1 0 1 2 is added to each sample. After 5% trifluoroacetic acid, each 1ml was divided into 10 times and treated with a reversed phase separation tube (BU-300, C4, 2.lx220mro, manufactured by Perkin-Elmer) equilibrated with 25% acetonitrile containing 0.1% trifluoroacetic acid. The solution was washed with a linear gradient solution of acetonitrile having a concentration of 55% within 60 minutes, and the flow rate was 0.2 m 1 per minute, and the peaks 6 and 7 were collected. Part of the obtained peak 6 and peak 7 fractions were analyzed using a protein sequence analyzer (professional specification type 494, manufactured by Perkin-Elmer) to analyze the N-terminal amino acid sequence analysis. Because the analysis was not possible, it is speculated that the end of the protein is likely Blocked. Therefore, the Chinese national standard (CNS) A4 specification (210X 297 mm) is applied to the paper size of this protein. 22 3 8 0 7 6 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 538049 A7 B7 5. Description of the invention (2 3 ) For internal amino acid sequence analysis. That is, the spike 6 and spike 7 fractions were respectively centrifuged and concentrated, and then 100 wg of dithiothreitol, 10 mM EDTA, 7M guanidinium acid, and 0.5M Tris-Hcl (pH8.5 containing CHAPS) were added. ) 50 / i 1, left at room temperature for 4 hours, after reduction, 0.2 ^ 1 of 4-vinylpyridine was added, and it was left overnight at room temperature to perform pyridyl ethylation. This sample 1 U 1 was added with 25% trifluoroacetic acid, and a reverse phase separation tube equilibrated with 20% acetonitrile containing 0.1% trifluoroacetic acid (BU-300, C4, 2.1x30mm, Perkin-E] mer product) treatment, and then a linear gradient solution of acetonitrile with a concentration of 50% within 30 minutes, and was washed at a flow rate of 0.3 m 1 per minute to obtain a 0 CIF sample for reducing pyridine ethylation. The samples were concentrated by centrifugation, and then dissolved with 8M urea and 0.1M Tris-Hcl (pH9) 25 / i 1 containing 0.1% Tween80, and then diluted with 73W1 of 0.1M Tris-Hcl (pH9). Then, add 0.02 / ig AP1 (_Aminolactone from Wako Pure Chemical Industries, Ltd.) and react at 37 ° C for 15 minutes. Add 1 / i 1 of 25% trifluoroacetic acid to the reaction solution, and treat it with a reverse phase separation tube (RP-300, C8, 2, IX 220mm, manufactured by Perkin-Elmer) equilibrated with 0.1% trifluoroacetic acid. The peptide fragment was obtained by dissolving in a linear gradient solution of acetonitrile with a concentration of 50% in 70 minutes at a flow rate of 0.2 ml per minute (see Figure 5). The obtained peptide fragments (p 丨 ~ P3) were analyzed for their amino acid sequences by a protein sequence analyzer, and the results are shown in the sequence listing in sequence numbers 1 to 3. [Example 7] The decree of the cDNA sequence

1 ) 由IMR-90細胞分離聚（A)+RNA (請先閱讀背面之注意事項再填寫本頁) 、1Τ 本紙張尺度適用中國國家標準（CNS ) Α4規格（210X 297公釐） 23 3 8 0 7 6 538049 A7 B7 五、發明説明（2 4 ) 使用Phast track inRNA分離組劑（Invitrogene公司製品）按照其指示分離得I M R _ 9 0細胞的聚（A )+ R N A。按照該方法從1 X 1 0 8個I M R - 9 0細胞中取得大約1 0 /i g的聚（A ) + R N A。 i i )混合引物之調製依據先前所得胜肽（序列表序列號碼2和3 )的胺基酸序列，合成下列二種混合引物，即合成可對胜肽P2(指序列號碼為2之胜肽）的第6個胺基酸（G 1 η )到第1 2個胺基酸（L e u )的胺基酸序列編碼之塩基序列的所有可能寡核t 酸混合物（混合引物No. 2F)。另外，合成可對胜肽P3(指序列號碼3的胜肽）的第6個胺基酸（H i s )到第1 2個胺基酸（ L y s )的胺基酸序列編碼的所有塩基序列的相補寡核酸混合物（混合引物，No. 3R)。所使用混合引物的塩基序列示於表3。 g_2_ =No . 2F = 經濟部中央標準局員工消費合作社印製1) Poly (A) + RNA is isolated from IMR-90 cells (please read the precautions on the back before filling this page), 1T This paper size applies the Chinese National Standard (CNS) A4 specification (210X 297 mm) 23 3 8 0 7 6 538049 A7 B7 V. Description of the invention (2 4) Using Phast track inRNA isolation kit (manufactured by Invitrogene) according to its instructions, poly (A) + RNA of IMR_90 cells was isolated. According to this method, about 10 / i g of poly (A) + R N A was obtained from 1 X 108 cells. ii) Preparation of mixed primers According to the amino acid sequences of the previously obtained peptides (sequence numbers 2 and 3 in the sequence listing), the following two mixed primers were synthesized, namely, peptide P2 (referred to as the peptide with sequence number 2) All possible oligonucleotide mixtures (Mixed Primer No. 2F) of the 6th amino acid (G 1 η) to the 12th amino acid (L eu) amino acid sequence encoded by the amino group. In addition, all sulfonyl sequences that can encode the amino acid sequence of the 6th amino acid (H is) to the 12th amino acid (L ys) of the peptide P3 (referring to the peptide of SEQ ID NO: 3) were synthesized. Of complementary oligonucleotide mixtures (mixed primers, No. 3R). The fluorenyl sequences of the mixed primers used are shown in Table 3. g_2_ = No. 2F = Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs

5 1 -CA AGAACAAA CTTTTCAATT-3 f G G G C C GC A G =N o . 3 R =5 1 -CA AGAACAAA CTTTTCAATT-3 f G G G C C GC A G = N o. 3 R =

5f-TTTATACATT GTAAAAGAAT G-3 f C G C G GCTG5f-TTTATACATT GTAAAAGAAT G-3 f C G C G GCTG

A C G 丁本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 3 8 0 7 6 (請先閱讀背面之注意事項再填寫本頁) 24 538049 A7 B7 五、發明説明（25 )A C G D This paper size applies to Chinese National Standards (CNS) A4 specifications (210X 297 mm) 3 8 0 7 6 (Please read the precautions on the back before filling this page) 24 538049 A7 B7 V. Description of the invention (25)

Hi)藉OCIFcDNA片段的PCR增殖由實施例7-ί)項所得聚（A)+RNA lag為模板，藉 Superscript IIcHDA合成組劑（吉勿可BRL公司製品），按照其指示合成單鎖cDNA，再使用該cDNA和實施例7-M)項所示引物進行PCR,而得OCIFcDNA片段。其條件如下所示 Ο l〇x Ex Taq緩衝液（日本寶酒造公司製品） 2 . 5inM dNTP 4 u 1 cDNA溶液 1 Μ 1Hi) Using the polymorphism (A) + RNA lag obtained from Example 7-ί) as a template by PCR proliferation of the OCIF cDNA fragment, and using the Superscript IIcHDA synthesis kit (made by Jebel BRL) to synthesize single-locked cDNA according to its instructions The cDNA and the primers shown in Example 7-M) were used to perform PCR to obtain an OCIF cDNA fragment. The conditions are as follows: 〇 l〇x Ex Taq buffer (manufactured by Nippon Brewery Co., Ltd.) 2.5 inM dNTP 4 u 1 cDNA solution 1 Μ 1

Ex Taq (寶酒造公司製品） 0· 25 w I 蒸餾水 2 9 · 7 5 μ 1 40 α Μ引物 No · 2F 5 “ 1 40“Μ引物 No*3R 5 u 1 經濟部中央標準局員工消費合作社印製 (請先閲讀背面之注意事項再填寫本頁) 將上述溶液在微量離心管中混合後，按照下述條件1 _ 行P C R。9 5 °C下前處理3分鐘後，重複9 5 1C 3 0秒鐘，5 0 °C 3 0秒鐘，7 0 °C 2分鐘之3階段反應3 0次後，在7 〇 °C下保溫5分鐘。將反應液之一部份進行瓊脂糖電泳分析，而確認獲得大約400bp的均一 DNA片段。 [實施例8 ] 由PCR所憎幅OCTPcDNAH段之純条增！〇〇其塩棊序列一之決宙將實施例7 - Π i )項所得0 C I F c D N A片段，依照M a r c h u k D.等人之方法（參考Nucleic acid Res· 19卷，1154頁， 1991年）利用DNA連接組劑Ver,2(寶酒造公司製品）插入質本纸張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 25 3 8 0 7 6 538049 A7 ______B7 _ _ 五、發明説明（2 6 ) feipBluesctipt II Sf(-(Stratagene公司製品），再進行大腸菌DH5a (吉勿可BRL公司製品）之形質轉換。增®所得形質轉換株，而依照常法精製而得插入有約4 0 0 b p的 OCIFcDNA片段之質粒。該質粒命名其為pBSOCIF。插入在該質粒的0 C I F c D H A Η段的塩基序列，藉T a q染料去氧終端子循環定序組劑（Perkin-Elmer公司製品）決定之。該〇 C I F c D ΝΑ之大小為3 9 7 b p。由該塩基序列所能預測的自1 3 2 個胺基酸所構成胺基酸序列中，分別在其N末端，C末端發現設計混合引物時所使用0 C I F内部胺基酸序列（序列表中，序列號碼2和3)存在。又在該由132個胺基酸所構成胺基酸序列中也能發現0 C I F的内部胺基酸序列（序列號碼1 )之存在。由上述結果，可確定所純条增殖的397bp的cDNA 為OCIFcDNA片段。 [實施例9 ] D N A探針夕調剪經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) 以實施例8所合成插人有3 9 7 b P的〇 C I F c D N A片段的質粒為模板，按照實施例7 M i i )項的條件下進行P C R ,而增幅該OCIFcDNAM段。藉瓊脂糖電泳而分離397bp的 OCIFcDNA片段後，使用QIAEX凝膠萃取組劑（吉阿研公司製品）精製之。該DNA用megapMme DNA標識組劑（Amersham公司製品）以[a 32P] dCTP標識，以其全長的IFcDN A提供篩選用探針用途。 [實施例1 0 ] c D N A瘇謳製本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 26 3 80 7 6 538049 A7 B7 五、發明説明67 ) 使用實施例7 -丨）項所得聚（A ) + R N A ,以其2 . 5 w g為模板，藉0^31：】6?^1^〇01^合成組劑（(：]〇以6(^公司製品）按照該公司之指示方法，使用ο 1 U 〇 ( d T )引物合成c D N A ,附加以E c 〇 R I - S a 1 I - N 〇 t - I附加物，進行c D N A形態級分，經乙醇沈澱處理後，溶解在1 0 /i 1的T E緩衝液中。所得有附加物之cDNA,取其O.lyg用T4DNA連接酶插人在事先經 EcoRI切斷的1μ g的λ ZAP表現載體（Strata-gene公司製品 )中。所得cDNA重組噬菌體DNA溶液，用Gigapack GoldII( Stratagene公司製品）提供活體外包裝（invitropackaging )反應，而調製得λΖΑΡ表現重組噬菌體。 [實施例1 1 ] 重纟日噬蘭體^篩潠經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) 實施例1 0所得重噬菌體在3 7 1C下以1 5分鐘感染處理大腸菌XLl-Blue MRF’（Strata-gene公司製品）後，添加在加溫至5 0 10的含有0 , 7 %洋菜的N Z Y培養基中，然後注入N Z Y 洋菜培養穴盤中，在37 °C下培養一夜後，産生溶菌斑的穴盤上，將Hi-bond(Amersham公司製品）密阽大約30秒鐘。將該濾器按照常法以鹼變性後，中和，浸在2 X S S C溶液後，藉UV crosslink(Stratagene公司製品）固定DNA在濾器上。所得濾器用含有1 0 0 w g / hi ]鮭魚精子0以的雜化緩衝液（Ex Taq (product of Takara Shuzo Co.) 0 · 25 w I Distilled water 2 9 · 7 5 μ 1 40 α Μ Primer No · 2F 5 "1 40" Μ Primer No * 3R 5 u 1 Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (Please read the precautions on the back before filling this page) After mixing the above solution in a microcentrifuge tube, perform 1_ PCR in accordance with the following conditions. After pretreatment at 95 ° C for 3 minutes, repeat 9 5 1C for 30 seconds, 50 ° C for 30 seconds, and 70 ° C for 2 minutes. The reaction in 3 stages is performed 30 times, at 70 ° C. Incubate for 5 minutes. A part of the reaction solution was analyzed by agarose electrophoresis, and it was confirmed that a uniform DNA fragment of about 400 bp was obtained. [Example 8] Pure strips of OCTPcDNAH fragments amplified by PCR! 〇〇 The sequence of the first sequence will be obtained in Example 7-Π i) 0 CIF c DNA fragment, according to the method of Marchuk D. et al. (Refer to Nucleic acid Res. 19, p. 1154, 1991) Use DNA linking agent Ver, 2 (product of Baoshuo Brewery Co., Ltd.) to insert the quality of the paper. The size of the paper is applicable to the Chinese National Standard (CNS) A4 (210X297 mm) 25 3 8 0 7 6 538049 A7 ______B7 _ _ 5. Description of the invention (2 6) feipBluesctipt II Sf (-(Stratagene)), and then transform the E. coli DH5a (Jibok BRL). The resulting transformant strain was added in accordance with the conventional method to insert about 4 0 0 bp The plasmid of the OCIF cDNA fragment. This plasmid was named pBSOCIF. The fluorenyl sequence inserted in the 0 CIF c DHA Η section of this plasmid was determined by the T aq dye deoxyterminator cycle sequencing kit (Perkin-Elmer). The size of the 〇CIF c D ΝΑ is 3 97 bp. The amino acid sequence composed of 132 amino acids that can be predicted from the amidine sequence is found at the N-terminus and the C-terminus of the design mix. 0 CIF used for primers A partial amino acid sequence (sequence numbers 2 and 3 in the sequence listing) exists. In the amino acid sequence composed of 132 amino acids, an internal amino acid sequence of 0 CIF (sequence number 1) can also be found From the above results, it was confirmed that the 397bp cDNA amplified from the pure strip was an OCIF cDNA fragment. [Example 9] DNA probe printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back first) (Fill in this page again.) Using the plasmid inserted with the OCIF c DNA fragment of 3 97 b P synthesized in Example 8 as a template, PCR was performed in accordance with the conditions of Example 7 M ii), and the OCIFcDNAM segment was amplified. The 397 bp OCIF cDNA fragment was separated by agarose electrophoresis, and then purified using QIAEX gel extraction kit (manufactured by Giya Research Co., Ltd.). The DNA was labeled with [a 32P] dCTP using megapMme DNA labeling kit (manufactured by Amersham), and provided with its full-length IFcDN A as a selection probe. [Example 1 0] c. The size of this paper produced by DNA is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm) 26 3 80 7 6 538049 A7 B7 V. Description of the invention 67) Use the results obtained in Example 7-丨) Poly (A) + RNA, using its 2.5 wg as a template, borrow 0 ^ 31:] 6? ^ 1 ^ 〇01 ^ synthetic agent ((:) 〇 to 6 (^ company products) according to the company's instructions Methods: c DNA was synthesized using ο 1 U 〇 (d T) primers, and E c 〇RI-S a 1 I-N 〇t-I was added to form the c DNA morphological fraction. After ethanol precipitation treatment, dissolve In TE buffer at 10 / i 1. The cDNA obtained with the add-on was taken from O.lyg and inserted into 1 μg of λ ZAP expression vector (Strata-gene Corporation) cut with EcoRI in advance using T4 DNA ligase. ). The obtained cDNA recombinant phage DNA solution was prepared with Gigapack GoldII (manufactured by Stratagene) to provide an invitropackaging reaction, and λZAP was expressed to express the recombinant phage. [Example 1 1] Re-examination of phage blue sieves Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (please read the notes on the back before filling in Page) Example 10 Inoculated the bacteriophages at 37 ° C for 15 minutes to treat coliforms XLl-Blue MRF '(manufactured by Strata-gene), and then added to 0, 7% ocean containing warming to 5 0 10 The NZY medium of the dish was poured into a NZY agar culture tray, and after incubating at 37 ° C overnight, the hi-bond (manufactured by Amersham) was densely packed on the tray that produced plaques for about 30 seconds. The filter was denatured with alkali in accordance with the usual method, neutralized, immersed in 2 XSSC solution, and the DNA was fixed on the filter by UV crosslink (manufactured by Stratagene). The obtained filter was used with 100 wg / hi] salmon sperm. Hybridization buffer

A m e r> s h a m公司製品）浸漬，在6 5 t下處理4小時後，移至添加有熱變性過的上述D ΝΑ探針（2 X 1 0 5 c p m / m ])的上述緩衝液中，在6 5 °C下雜交處理一夜。反應後，濾器用2 X S S C 溶液2次，用0 . 1 X S S C , 0 · 1 % S D S溶液2次，分別在6 5 °C 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 27 3 8 0 7 6 538049 A7 B7 經濟部中央標準局員工消費合作社印製五、發明説明（28 ) 下洗淨1 0分鐘。所得若干呈陽性反應之純条再進行2次篩選而純化之。從其中選擇具有約1 . 6 k b的插入部分做為以下用途。該純化的噬菌體稱為λ 0 C I F。純化的λ 0 C I F依照 λΖΑΡ表現純条組劑（Stratagene公司製品）和其指示，感染大腸菌X L 1 - B 1 u e M R F 1後，再用輔助噬鐘體E X A s s丨s t ( S t「a t a g e n e公司製品）進行多重感染，將其培養上澄液感染大腸菌X L 0 L R ( S t r a t a h e n e公司製品）之後，選取康黴素耐性株而獲得在pBKCMV(Stratagene公司製品）插人有上述 1 . 6kb的質粒pBKOC IF的形質轉換株。該形質轉換株以 PBK/01F10命名，並寄存在日本通商産業省工業技術院生命工學工業技術研究所，其寄存號碼為F E R Μ B P - 5 2 6 7 (自平成7年10月25日起依照布達佩斯條約的寄存移管方法，由FERM Ρ-14998的原有寄存轉寄存）。增殖具有該質粒的形質轉換株，並按照常用方法精製質粒。 [實施例12] 編碼0 C I F的總胺某酴序列的c D Ν Α的塩某序列之決定將實施例1 1所得0 C I F c D N A的塩基序列藉T a q染料去氣終端子循環定-序組劑（P e r k i η - E 1 m e r公司製品）決定之。所用引物乃依據T3 , T7引物（Stratagene公司製品）和 0 C I F c D N A的塩基序列所設計的合成引物，其序列示於序列表中序列號碼1 6〜2 9。所決定的0 C I F的塩基序列以序列號碼6 ,由其序列所推測的胺基酸序列以序列號碼5分別表示之。 [實施例1 3 ] (請先閱讀背面之注意事項再填寫本頁) 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 28 3 8 0 7 6 538049 A7 B7 五、發明説明（29 )A me r > product of sham company) immersion, after processing at 65 t for 4 hours, moved to the above buffer solution with the thermally denatured D ΝΑΝ probe (2 X 105 cpm / m]), Hybridize overnight at 65 ° C. After the reaction, the filter was applied twice with 2 XSSC solution, and twice with 0.1 XSSC and 0.1 · 1% SDS solution, respectively at 65 ° C. This paper size is in accordance with Chinese National Standard (CNS) A4 (210X 297 mm) 27 3 8 0 7 6 538049 A7 B7 Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs 5. The description of the invention (28) is washed for 10 minutes. The obtained pure positive strips were purified by further screening. An insertion portion having about 1.6 kb was selected therefrom for the following purposes. This purified phage is called λ 0 C I F. The purified λ 0 CIF was expressed in accordance with λZOAP as a pure stripe preparation (manufactured by Stratagene) and its instructions. After infection with coliform XL 1-B 1 ue MRF 1, it was then treated with the auxiliary phage EXA ss 丨 st (products of atagene ) After multiple infections, the culture supernatant was infected with E. coli XL 0 LR (manufactured by Stratahene), and then a concomycin-resistant strain was selected to obtain pBKCMV (manufactured by Stratagene) with the above-mentioned 1.6 kb plasmid pBKOC IF The transformant strain named "PBK / 01F10" and deposited in the Institute of Life Science and Industrial Technology of the Institute of Industrial Technology, Ministry of International Trade and Industry, and its deposit number is FER Μ BP-5 2 6 7 (Since 2007 Starting from October 25, the deposit transfer method according to the Budapest Treaty was transferred from the original deposit of FERM P-14998). The transformant with the plasmid was propagated, and the plasmid was purified according to the usual method. [Example 12] Code 0 CIF The determination of the sequence of c D Ν Α of the total amino amine sequence is determined by cyclically determining the amino group sequence of the 0 CIF c DNA obtained in Example 11 by using the aq dye deaeration terminal. -Sequencer (Perki η-E 1 mer company) decided. The primers used are synthetic primers designed based on T3, T7 primers (Stratagene company) and 0 CIF c DNA fluorenyl sequence, whose sequence is shown in the sequence Sequence numbers 1 6 to 2 in the list. The determined 0 CIF fluorenyl sequence is represented by sequence number 6, and the amino acid sequence inferred from the sequence is represented by sequence number 5. [Example 1 3] (please first Read the notes on the reverse side and fill out this page) This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) 28 3 8 0 7 6 538049 A7 B7 V. Description of the invention (29)

苗2 9 3 / E B 細朐生産重紐型0 C T F 1 ) 調製OCIFcDNA的表現質粒實施例1 1中所得插人有約1 . 6 k b 0 C I F c D N A的質粒 pBKOCIF用限制酶BamHI和Zhol消化，切割得OCIFcDNA,用 ®脂糖電泳法分離後，使用Q I A E Z凝_萃取組劑（吉阿研公司製品）精製之。將此0 C I F c D N A使用接合用組劑V e r · 2 (寶酒造公司製品）插人在事先經限制酶B a in Η I和Z h ο I消化而成的表現質粒pCEP4(Invitogene公司製品），而進行大腸菌 I) Η 5 α (吉勿可B R L公司製品）之形質轉換。所得形質轉換株經増®，將插人有OCIFcDNA的表現質粒pCEPOCIF用吉阿研分離管（吉阿研公司製品）精製之。用乙醇處理0CIF表現質粒PCEP0CIF使之沈澱後，再用無菌蒸餾水溶解偽提供下述操作用途。 i i ) 0 C I F c 1) N A的短暫表現和其活性之測定經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) 使用實施例1 3 - ί )項所得0 C I F表現質粒p C E P 0 C I F ,按下述方法表現重組0 C I F ,並測定其活性。在6洞穴盤的各洞孔中含有1 0 %胎牛血清（吉勿可81?1^公司製品）的^08培養基中，播以8X 105個293/ΕΒΝΑ細胞（Invitogene公司製品），翌日去除培養基後，用無血清IMDM培養基洗淨細胞。穿染用試藥脂性穿染胺（吉勿可B R L公司製品）依照隨附指示，事先用0PTI-MEM培養基（吉勿可BRL公司製品）稀釋而成的p C E P 0 C I F和脂性穿染胺混合後，加入該混合液於上述穴盤各洞孔中之細胞上。上述所用pCEPOCIF和脂性穿染胺之份量分別為3 /i g和1 2 u U 3 8小時後去除培養基，加本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 29 3 8 0 7 6 538049 Α7 Β7 經濟部中央標準局員工消費合作社印製五、發明説明（3 0 ) 入1 m 1的新鮮0 P T卜Μ E Μ培養基，再於3 0小時後回收培養基，提供0 C I F活性測定用試料。0 C I F之活性測定乃按下述方法進行。先後約1 7日的鼠骨髓細胞在活化型維生素D 3之共存下，將破骨細胞形成以酒石酸耐性酸性磷酸酯酶活性誘導進行試驗而測定其抑制活性，做為0 C I F之活性。換言之，在9 6洞的微穴盤中放入用含有2 X 1 0 — 8 Μ活化型維生素D 3和 1 0 %胎牛血清的α - Μ Ε Μ培養基（吉勿可B R L公司製品）稀釋過的試料100/il,然後將先後約17日的鼠骨髓細胞3Χ105 個用含有1 0 %胎牛血清1 0 0 μ I的ex - Μ E Μ培養基懸濁後播種之。在5 %的二氧化碩，3 7 °C , 1 0 0 %濕度下培養一星期。培養第3日和第5日，廢棄1 6 0 μ 1的培養液，添加用含有 IX 10_8Μ的活化型維生素D3和10%胎牛血清的cx -MEM培養基所稀釋的試料1 6 0 α 1。培養7日後，用磷酸塩緩衝生理食塩水洗淨，再以乙醇/丙酮（1 : 1 )溶液於室溫下固定細胞一分鐘，再利用酸性磷酸酯酶活性測定組劑（A c i d Phospatase, Leucocyte,型錄 No.387_i\, Sigma公司産品 )染色而檢驗其破骨細胞形成活性。以酒石酸共存下的酸性磷酸酯酶活性陽性細胞減少程度做為〇 C I F活性。其結果如表4中所示，確認該培養液具有和先前從I M R - 9 0的培養液中所得天然型0 C I F用同樣活性存在。 (請先閱讀背面之注意事項再填寫本頁) 罐衣· 訂 d 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 30 3 8 0 7 6 538049 Α7 Β7 五、發明説明（31 )Miao 2 9 3 / EB cell line production of heavy button 0 CTF 1) Modified expression plasmid of OCIFcDNA The plasmid pBKOCIF obtained in Example 11 with about 1.6 kb 0 CIF c DNA was digested with restriction enzymes BamHI and Zhol, The OCIFcDNA was cut and separated by lipolipid electrophoresis, and then purified using QIAEZ Coagulation Extraction Kit (manufactured by Ji'a Research Co., Ltd.). The expression plasmid pCEP4 (manufactured by Invitogene), which was digested with restriction enzymes B a in Η I and Z h ο, was inserted into this 0 CIF c DNA using the combination reagent Ver er 2 (product of Takara Shuzo Co., Ltd.), The transformation of coliform I) Η 5 α (product of Jebel BRL) was performed. The obtained shape-converting strain was purified by Gyalco separation tube (manufactured by Gyalka Co., Ltd.) by inserting the expression plasmid pCEPOCIF into which OCIFcDNA was inserted through 増 ®. The 0CIF expression plasmid PCEP0CIF was treated with ethanol to precipitate it, and then dissolved with sterile distilled water to provide pseudo operation. ii) 0 CIF c 1) Measurement of NA's short-term performance and its activity Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (Please read the precautions on the back before filling this page) Use Example 1 3-ί) 0 CIF expressed plasmid p CEP 0 CIF, and recombinant 0 CIF was expressed according to the following method, and its activity was measured. 8X 105 293 / EΒΝΑ cells (manufactured by Invitogene) were seeded in ^ 08 medium containing 10% fetal bovine serum (Jibek 81? 1 ^ company product) in each hole of the 6-hole plate, and removed the next day. After the medium, the cells were washed with serum-free IMDM medium. Fatty dyes for transfection dyes (Gerbic BRL) are mixed with p CEP 0 CIF diluted with 0PTI-MEM medium (Geber BRL's products) in advance. Then, the mixed solution was added to the cells in each hole of the aforementioned tray. The amount of pCEPOCIF and fatty pentaamine used above is 3 / ig and 1 2 u U 3 respectively. After 8 hours, the medium is removed, and the paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) 29 3 8 0 7 6 538049 Α7 Β7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (30) Put 1 m 1 of fresh 0 PT BM E EM medium, and recover the medium after 30 hours to provide 0 CIF activity measurement Use the sample. 0 C I F activity was measured by the following method. In the presence of activated vitamin D 3 in about 17 days, rat bone marrow cells were induced to undergo osteoclast formation with tartaric acid-resistant acid phosphatase activity, and the inhibitory activity was determined as 0 C I F activity. In other words, a 96-well micro-dish was placed in an α-M E M medium (made by Jebel BRL) containing 2 X 1 0-8 M activated vitamin D 3 and 10% fetal bovine serum. After the test sample was 100 / il, 3 × 105 mouse bone marrow cells, which were about 17 days old, were suspended in ex-M E M medium containing 10% fetal bovine serum and seeded. Incubate for one week at 5% SO2, 37 ° C, 100% humidity. On the 3rd and 5th day of culture, 160 µl of the culture medium was discarded, and a sample 16 0 α 1 diluted with a cx-MEM culture medium containing IX 10-8M of activated vitamin D3 and 10% fetal bovine serum was added. After 7 days of incubation, the cells were washed with phosphate buffered saline and then washed with ethanol / acetone (1: 1) solution at room temperature for one minute. The acid phosphatase activity assay group (A cid Phospatase, Leucocyte) , Catalog No. 387_i \, Sigma product) staining to test its osteoclast formation activity. The degree of decrease in acid phosphatase-positive cells in the presence of tartaric acid was defined as 0 C I F activity. As a result, as shown in Table 4, it was confirmed that the culture solution had the same activity as the natural type 0 C I F obtained from the culture solution of IM R-90 previously. (Please read the precautions on the back before filling in this page.) Cans · Ordering d This paper size is applicable to Chinese National Standard (CNS) A4 (210X 297 mm) 30 3 8 0 7 6 538049 Α7 Β7 V. Description of the invention ( 31)

m 4 用293/RBN/\^ _所表現偯泰液中之OCIF活件稀釋率 1/20 1/40 1/80 1/160 1/320 1/640 1/1280 導入0CIF 基因 ++ ++ + + 導入載體 - - - 未處理 - 一 _ (表中，+ +示破骨細胞形成受到80%以上抑制之活性， +示破骨細胞形成受到3 0〜8 0 %抑制之活性，-示無法檢驗出活性）。 i i i ) 2 9 3 / E B N細胞由來重組型0 C I F之精製經濟部中央標準局員工消費合作社印製 (請先閲讀背面之注意事項再填寫本頁) 實施例1 3 - i i )項所記載的2 9 3 / E B N A細胞經大量培養而得培養液1 · 8兑中，加入C Ο P S使成為0 · 1 %濃度，再經〇.22“111的濾器（^<111丨1〇广6公司製品，$七01^匕6(^〇$)過濾後，以用1 0 m Μ T r i s - H c 1 ( p Η 7 · 5 )平衡過的5 0 m 1肝素•瓊脂糖CL-6B分離管（2·6Χ IOcib, Pharmacia公司製品）處理之。用含有 0.1%CHAPS 的 10mM Tris-Hcl(pH7.5)洗淨後，以 100分鐘内成為2M濃度的直線梯度的氯化鈉溶液，按照每分鐘4 m 1的流速溶洗，以每餾分8 1進行級分。各餾分取其 1 5 0 /i 1 ,按照實施例2所示方法測定其〇 C I F活性，而獲得在約0 · 6〜1 ♦ 2 Μ氯化銷溶液所得出的具有〇 C I F活性的纟留分 1 1 2πι 1 〇本紙張尺度適用中國國家標準（CNS ) Α4規格（210'乂297公釐） 3 1 3 8 07 6 538049 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明（32 ) 所得上述0 C I F活性餾分1 1 2 m 1，以含有0 ♦ 1 % c H A p s的 l〇mM Tris-Hcl(pH7.5)稀釋成為l〇00ml後，利用以含有 CHAPS的ΙΟπιΜ Tris-Hcl(pH7.5)平衡過的親和性分離管（肝素-5PW, 〇,8x7.5cm, Tosoh公司製品）處理之。用含有 0.1%CHAPS的 lOmM Tris-Hcl(pH7.5)洗淨後，以分鐘内成為2M濃度的氯化鈉直線梯度溶液，按照每分鐘 0 · 5 m 1的流速進行溶洗，依照每餾分〇 · 5 ία 1進行級分。所得各餾分各取其4 /i 1 ,按照實施例4中所示方法在還原和非還原條件下進行SDS -聚丙烯醯胺凝膠電泳分析。其結果餾分30〜32在還原條件下檢驗得約60kD的0CIF帶，在非還原條件下檢驗得約6 0 k D和約1 2 0 k D的0 C I F帶出現。因此，收集餾分3 0〜3 2 ,做為純化2 9 3 / E B N A細胞由來重組型〇 C I F ( r 0 C I F ( E ))級分。以B S A為標品，用羅利測定蛋白質之結果。確知獲得535/ig/ml的rOCIF(E)1.5ml。 [實施例14] 由C Η 0細朐牛産重組型Π C T F i ) 調製0CIF的表現質粒實施例1 1中所得插人有約1 . 6 k D的0 C I F c D Ν Α的質粒 p B K 0 C I F以限制酶S a 1 I和E c 〇 R V消化，切割得約1 . 4 k b的 0 C I D c D Η A片段，用瓊脂糖電泳法分離後，使用Q I A E X凝_ 萃取組劑（吉阿研公司製品）精製之。另外，將表現載體 pcDL-SRa 296(參考 Malecular and Cellular Biology, 第8卷，4 6 6 - 4 7 2頁，]9 8 8年）以限制_ P s t I和K p η I消化後 ,將其約3 . 4 k b的表現載體D N A片段用瓊脂糖電泳法分離後 (請先閱讀背面之注意事項再填寫本頁) 衣‘ 4 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 32 3 8 0 7 6 538049 A7 _ B7_ ___ 五、發明説明（33 ) ，再用Q I A E X凝顧萃取組劑（吉阿研公司製品）精製之。使用DNA鈍端化組劑（寶酒造公司製品）將上述精製好的〇 C I F e D N A片段和表現載體D N A片段的末端加以鈍端化處理。繼之，使用連接組劑Ver.2(寶酒造公司製品），插入〇 C I F c D N A Μ段在經鈍端化過的表現載體D N A H段上，進行大腸_DH5ot (吉勿可BRL公司製品）的形質轉化，而獲得具有0CIF表現質粒pSRa 0CIF的轉化株。 i i )表現質粒之調製實施例13M)項所得具有0CIF表現質粒pSRa 0CIF的轉化株和W092/01053號公報所示之具有鼠DHFR基因表現質粒 p B A d D S V的轉化株分別按照常法加以增殖，再依據/m 4 Use 293 / RBN / \ ^ _ to show the dilution ratio of OCIF jobs in Huatai solution 1/20 1/40 1/80 1/160 1/320 1/640 1/1280 Import 0CIF gene ++ ++ + + Introduction vector---untreated-_ (In the table, + + shows the activity of osteoclast formation inhibited by more than 80%, + shows the activity of osteoclast formation inhibited by 30 to 80%,-shows Unable to detect activity). iii) 2 9 3 / Origin of EBN cells Recombinant 0 CIF Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling out this page) Example 1 3-ii) 2 9 3 / EBNA cells were cultured in large quantities to obtain a culture solution of 1.8%. Adding C 0 PS to a concentration of 0.1%, and then passing through a 0.22 "111 filter (^ &111; 111 丨 1. 6 company). The product was filtered at $ 70, 01 ^ 6 (^ 〇 $), and separated with 50m 1 heparin • agarose CL-6B equilibrated with 10 m Μ Tris-H c 1 (p Η 7 · 5). Tube (2 · 6X IOcib, manufactured by Pharmacia). After washing with 10 mM Tris-Hcl (pH 7.5) containing 0.1% CHAPS, it becomes a 2M concentration linear gradient sodium chloride solution within 100 minutes. The solution was washed at a flow rate of 4 m 1 per minute, and fractions were fractionated at 81 per fraction. Each fraction was taken at 150 / i 1, and its OCIF activity was measured according to the method shown in Example 2 to obtain about 0.6 ~ 1 ♦ Retained fraction with 〇CIF activity obtained from 2 M chlorinated pin solution 1 1 2πι 1 〇 This paper size applies Chinese National Standard (CNS) Α4 specification (21 0 '乂 297 mm) 3 1 3 8 07 6 538049 A7 B7 printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the Invention (32) The above 0 CIF active fraction 1 1 2 m 1 was obtained to contain 0 ♦ 1 % c HA ps was diluted with 10 mM Tris-Hcl (pH 7.5) to 1,000 ml, and then the affinity separation tube (heparin-5PW, 〇) was equilibrated with 10 μM Tris-Hcl (pH 7.5) containing CHAPS. , 8x7.5cm, manufactured by Tosoh Co., Ltd.) After washing with 10 mM Tris-Hcl (pH 7.5) containing 0.1% CHAPS, it becomes a 2M concentration sodium chloride linear gradient solution within minutes. The solution was washed at a flow rate of 5 m 1 and fractions were fractionated according to 0.5 ία 1. Each fraction obtained was 4 / i 1, and SDS was performed under reducing and non-reducing conditions according to the method shown in Example 4. Polyacrylamide gel electrophoresis analysis. As a result, fractions 30 to 32 were examined under the reducing conditions to obtain a 0CIF band of about 60 kD, and non-reducing conditions were examined to obtain a 0 CIF band of about 60 k D and about 120 k D. Therefore, the fractions 30 to 32 were collected for purification, and the recombinant type 0CIF (r 0 CIF (E)) derived from EBNA cells was obtained. Minute. Using B S A as the standard, the results were determined by Raleigh. It was confirmed that 1.5 ml of rOCIF (E) was obtained at 535 / ig / ml. [Example 14] Recombinant Π CTF i produced by CΗ0 fine yak was used to modulate the expression plasmid of 0CIF. The plasmid p BK with 0 CIF c D Ν Α obtained by inserting about 1.6 k D was inserted in Example 11. 0 CIF was digested with the restriction enzymes Sa 1 I and E c 〇RV, and about 1.4 kb of 0 CID c D Η A fragment was cut. After separation by agarose electrophoresis, QIAEX coagulation_extraction group (Gia Research company products) refined. In addition, the expression vector pcDL-SRa 296 (refer to Malecular and Cellular Biology, Vol. 8, pp. 4 6 6-4 72,] 9 8 8 years) was restricted to digest _ P st I and K p η I, and The approximately 3.4 kb expression vector DNA fragment was separated by agarose electrophoresis (please read the precautions on the back before filling out this page). The size of this paper applies the Chinese National Standard (CNS) A4 specification (210X297 mm) ) 32 3 8 0 7 6 538049 A7 _ B7_ ___ V. Description of the invention (33), and then refined with QIAEX coagulation extraction agent (product of Ji'a Research Co., Ltd.). The ends of the purified OC I F e D N A fragment and the expression vector D N A fragment were subjected to blunt end treatment using a DNA blunting kit (manufactured by Takara Shuzo Co., Ltd.). Next, the linker Ver. 2 (product of Takara Shuzo Co., Ltd.) was used to insert 〇CIF c DNA Μ segment on the blunt-terminated expression vector DNAH segment to perform the shape of large intestine _DH5ot (product of Jebel BRL) Transformed to obtain a transformant with the 0CIF expression plasmid pSRa 0CIF. ii) Expression plasmid preparation Example 13M) The transformant obtained with the 0CIF expression plasmid pSRa 0CIF and the transformant with the mouse DHFR gene expression plasmid p BA d DSV shown in W092 / 01053 are proliferated according to the usual method. Re-based /

Maniatis 等人的方法（參考 Malecular Cloning,第 2 販）以鹼性方法和聚乙二醇方法處理，經氯化鉋密度梯度離心法精製之。 i i i ) C Η 0 d h F r —細胞在不含蛋白質培養基中的馴化處理經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) 在含有10%胎牛血清（吉勿可^[公司製品）的^0»培養基（吉勿可BRL公司製品）中繼代培養的CHOdhFr-細胞（ ATCC-CRL9096)，經過無血清培養基EX-Cell301(JRH B i 〇 s c i e n c e公司製品）馴化後，改利用不含蛋白質培養基 EX-細胞PFCH0(JRH Bioscience公司製品）馴化之。 i v )導人0 C I F表現質粒和D H F R表現質粒到C Η 0 d h F r —細胞中使用實施例1 4 - i i )項所調製〇 C I F表現質粒p S R α 0 C I F 以及D H F R表現質粒p B A d D S V ,利用下述電穿孔法（ Electroporation)將實施例 14~iii)項中所調製的 CHOdhFr- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 33 3 8 0 7 6 經濟部中央標準局員工消費合作社印製 538049 A7 B7 五、發明説明（3 4 ) 細胞加以轉化。將2 0 0 a g的P S R α 0 C I F質粒和2 Ο μ g的口8為(^$¥質粒以含有10%胎牛血清（吉勿可81^公司製品）的 I M D Μ培養基（吉勿可B R L公司製品）0 . 8 m 1在無菌條件下加以溶解後，再將2X107個的CHOdhFr —細胞浮游在上述0.8ml 培養液中。將該細胞浮游液放置容器（B i 〇 r a d公司製品）中，使用基因脈衝儀（Genepulser, Biorad公司製品），在 3 6 0 V , 9 6 0 a F的條件下藉電穿孔法進行轉化。裝有1 〇 m 1的 EX -細胞PF CH0培養基的浮游細胞用T型燒瓶（住友 B a k e 1 i t e公司製品）中，移入上述經過電穿孔法處理的細胞浮游溶液，在二氧化磺保溫箱中培養2日。使用E X -細胞PF CH0培養基，以5 0 0 0細胞/洞的濃度播種在96洞的微穴盤中，大約培養2星期。由於EX -細胞PF_CH0培養基不含有核酸，因此，母株的C Η 0 d h F r —無法在上述培養基中增殖，表現D H F R的細胞株得以選擇出來。由於使用〇 C I F表現質粒為D H F R表現質粒的1 0倍量，所以能表現D H F R的細胞株的大部分都會表現0 C I F。從所得量現D H F R的細胞株中，依據實施例2中所示測定方法，篩選得培養上澄液中〇 C I F活性高的細胞株。就所得0 C I F高生産株，利用Ε X -細胞Ρ Ρ C Η 0培養基以限界稀釋法進行細胞之純条增殖而穫得〇 C I F 高生産株5 5 6 1。 ν ) 重組型0 C I Ρ之生産為生産重組型0 C I F ( r 0 C I F )，接種C Η 0細胞（5 5 6 1 )於 Ε X -細胞3 0 1培養基3 il中，其細胞量為1 X 1 〇 5細胞/ m 1。使用史賓納燒瓶在3 7 °C下培養4〜5日。當細胞濃度增加到大 (請先閱讀背面之注意事項再填寫本頁)The method of Maniatis et al. (Refer to Malecular Cloning, No. 2) was treated by alkaline method and polyethylene glycol method, and purified by chlorinated planer density gradient centrifugation. iii) C Η 0 dh F r — Cell domestication in protein-free medium Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling this page) In the case of 10% fetal bovine serum ( JI0 ^ [company products] ^ 0 »medium (products of JI BIKE BRL company) subcultured CHOdhFr- cells (ATCC-CRL9096), and passed through serum-free medium EX-Cell301 (products of JRH Bioscience Co., Ltd.) ) After acclimatization, use protein-free medium EX-cells PFCH0 (made by JRH Bioscience) to acclimate it. iv) Introduce 0 CIF expression plasmid and DHFR expression plasmid to C Η 0 dh F r-Cells were prepared as described in Example 14-ii). CIF expression plasmid p SR α 0 CIF and DHFR expression plasmid p BA d DSV Use the following electroporation method to adjust the CHOdhFr prepared in items 14 to iii)-This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) 33 3 8 0 7 6 Central Ministry of Economic Affairs Printed by the Consumer Bureau of Standards Bureau 538049 A7 B7 V. Description of invention (34) Cells are transformed. 2 0 ag of PSR α 0 CIF plasmid and 2 0 μ g of mouth 8 were used as the (^ $ ¥ plasmid in 10% fetal bovine serum (Jibok 81 ^ company's product) IMD M medium (Jibok BRL) After the product was dissolved in 0.8 m 1 under sterile conditions, 2 × 107 CHOdhFr cells were floated in the above 0.8 ml culture solution. The cell suspension was placed in a container (product of Biorad Corporation), Gene pulser (Genepulser, manufactured by Biorad) was used for transformation by electroporation under conditions of 360 V, 960 a F. For planktonic cells containing 10 m 1 of EX-cell PF CH0 medium The T-flask (manufactured by Sumitomo Bake 1ite Co., Ltd.) was transferred to the above-mentioned electrophoretic cell floating solution and cultured in a sulfur dioxide incubator for 2 days. EX-cell PF CH0 medium was used at 5 0 0 0 The cell / hole concentration was seeded in a 96-well micro-well plate and cultured for about 2 weeks. Since the EX-cell PF_CH0 medium does not contain nucleic acid, the C Η 0 dh F r of the mother plant cannot be propagated in the above medium, showing DHFR cell lines were selected. Since the use of the 0CIF expression plasmid is 10 times the amount of the DHFR expression plasmid, most of the cell lines capable of expressing DHFR will express 0 CIF. From the obtained cell lines of present DHFR, the measurement method shown in Example 2 was used. The cells with high CIF activity in the culture supernatant were selected. From the obtained 0 CIF high-producing strains, the pure strips of the cells were propagated by the limiting dilution method using EX-cell P P C Η 0 medium to obtain 0 CIF high. Production strain 5 5 6 1. ν) Production of recombinant 0 CI RP is to produce recombinant 0 CIF (r 0 CIF), and inoculate C Η 0 cells (5 5 6 1) in E X -cell 3 0 1 medium 3 il The cell mass was 1 X 105 cells / m1. Incubate for 4 to 5 days at 37 ° C using a Spinner flask. When the cell concentration increases to large (please read the notes on the back before filling this page)

、1T 本紙張尺度適用中國國家標準（CNS ) Α4規格（210Χ297公釐） 34 3 8 0 7 6 〇〇49 A7 B7 …發明説明（35 ) 約1 y， 1 X 1 〇 6細胞/ m 1時，回收大約2 . 7 A的培養基。再加入約 2 (請先閱讀背面之注意事項再填寫本頁) ·7A的EX>細胞301培養基，重複培養。利用三個史賓納 _ $培養，生産約2 0 ft的培養液。、 1T This paper size is in accordance with Chinese National Standard (CNS) A4 specification (210 × 297 mm) 34 3 8 0 7 6 〇49 A7 B7… Description of the invention (35) Approx. 1 y, 1 X 1 〇6 cells / m 1 hour Recover approximately 2.7 A of culture medium. Add about 2 (please read the precautions on the back before filling out this page). • EXA 7A Cell 301 Medium and repeat the culture. Using three Spinner_ $ cultures, approximately 20 ft of culture fluid was produced.

Vl) cH〇細胞由來的重組型0CIF的精製由實施例1 4 - ( v )項所得1 β的培養液中，加入C H A P S使成為〇,1%濃度，再經〇.22"111的濾器（51^^^6(^0$, Milli-p〇re 公司製品）過濾後，以用 10mM Tris-Hcl(pH7.5 }平衡過的50ml肝素♦瓊脂糖FF分離管（2.6x10cm, Pharmacia公司製品）處理之。用含有0.1% CHAPS的lOmM Tpis〜Hcl(PH7.5)洗淨後，再用1〇〇分鐘内成為2M濃度的氯化鈉直線梯度溶液，以每分鐘4 m 1的流速溶洗，按每織分 8ml進行級分。各餾分以其150wl按照實施例2所示方法測定其0 C I F活性，獲得在約0 . 6〜1 · 2 Μ處溶洗出來的0 C I F 活性餾分1 1 2 m 1。經濟部中央標準局員工消費合作社印製將所得11 2 m 1的0 C I F活性餾分，用含有0 · 1 % C H A P S的 ΙΟιηΜ Tris-Hcl(pH7.5)稀釋成為 1200ml 後，再用含有 0.1 %(：(^?5的10—1>丨5-^1(9[17.5)平衡過的親和性分離管（籃色条-5PW, 0.5x5cm, Tosoh公司製品）處理之。用含有〇.1%(^^$的1〇1^1>丨3-1^1(?>[17.5)洗淨後，以90分鐘内成為3M濃度的氯化鈉直線梯度溶液，依照每分鐘〇·5ιη1的流速溶洗，按每餾分0 . 5 in 1進行級分。所得各餾分各取其4 w 1 ,按照實施例4中所示方法在還原和非還原條件下，進行S 1) S -聚丙烯醯胺凝膠電泳。其結果餾分30〜38在還原條下撿驗得約60kD的0CIF帶。在非 3 8 0 7 6 本紙張尺度適用中國國家標準（CNS ) A4規格（210 X297公釐） 35 538〇49Vl) Purification of recombinant 0CIF derived from cH0 cells. The 1 β culture obtained in item 14-(v) was added to CHAPS to a concentration of 0.1%, and then passed through a filter of 0.22 " 111 ( 51 ^^^ 6 (^ 0 $, manufactured by Milli-Pore), filtered to 50ml heparin equilibrated with 10mM Tris-Hcl (pH7.5} ♦ Sepharose FF separation tube (2.6x10cm, manufactured by Pharmacia) ) Treatment. After washing with 10 mM TPIs ~ Hcl (PH7.5) containing 0.1% CHAPS, and then a linear gradient solution of sodium chloride 2M concentration in 100 minutes, dissolved at a flow rate of 4 m 1 per minute Washed, fractions were made at 8 ml per weave. Each fraction was measured at 0 CIF with 150wl according to the method shown in Example 2 to obtain 0 CIF active fraction 1 which was dissolved and washed out at about 0.6 to 1.2 M. 1 2 m 1. Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs. The obtained 0 CIF active fraction of 11 2 m 1 was diluted with ΙΟιηΜ Tris-Hcl (pH 7.5) containing 0.1% CHAPS to 1200 ml. Affinity separation tube (basket color bar-5PW, 0.5x5cm, manufactured by Tosoh Co., Ltd.) with a balance of 0.1% (: ^? 5 of 10-1 > 丨 5- ^ 1 (9 [17.5) ) Treatment. After washing with 0.1% (^^ $ of 〇1 ^ 1 > 丨 3-1 ^ 1 (? &Gt; [17.5), it becomes a 3M sodium chloride straight line within 90 minutes. The gradient solution was washed at a flow rate of 0.5 μm per minute, and fractions were fractionated at 0.5 in 1. Each fraction obtained was 4 w 1 each, and was subjected to reducing and non-reducing conditions according to the method shown in Example 4. Then, S 1) S-polyacrylamide gel electrophoresis was performed. As a result, fractions 30 to 38 were examined under reduced strips to obtain a 0CIF band of about 60 kD. For non- 3 8 0 7 6 paper standards, Chinese national standards ( CNS) A4 size (210 X297 mm) 35 538〇49

、發明説明（3 6 ) (請先閱讀背面之注意事項再填寫本頁) 胃_條件下檢驗得約6 0 k D和約1 2 0 k D的0 C I F帶。因此，收 __分30〜38精製，做為CHO細胞由來重組型OCIF[rOCIF( e }]餾分。使用B S A為標準藉羅利法進行蛋白定量結果，確知1 獲得 113/i g/ml濃度的 rOCIF(C)4.5rol。 [寶施例1 5 ] 重組型0 C T F的N 末端耩诰分析將 3/i g的精製 rOCIF(E)和 rOCIF(C)用 Prospin( Perkin-Eiffle「公司製品）固定在聚偏二氟乙烯（PVDF)膜上，用2 〇 %的甲醇洗淨後，使用蛋白質序列分析儀（專利規格 49 2型，Perkin-Elmer公司製品）進行Η末端胺基酸序列分 $。其結果示於序列表中之序列號碼7。經濟部中央橾準局員工消費合作社印製 rOCIF(E)和rOCIF(C)的Ν末端胺基酸乃序列表中序列號碼5所記載胺基酸序列翻譯起點Met起第22個的Glu,由 M e t至G 1 η的2 1個胺基酸已知為訊息胜肽（S i g n a 1 p e p t i d e ) 。另外，由IMR-90培養液中精製而得天然型〇CIF的N末端胺基酸序列無法分析，據推測偽N末端的G 1 在培養中或精製過程中可能轉變為焦谷胺酸（Pyroglutanric acid)所造成。 [實施例16] 重邰型（r ) (1 C T F和丟然型（η ) (1 C I F之生物學活生-i ) 在鼠骨髄細胞条中由維生素Ds所誘導破骨細胞形成之抑制用含2 X 1 0 - 8 Μ活化型維生素D 3和1 〇 %胎牛血清的α -MEM培養基（吉勿可BRL公司製品），將所精製rOCIF(E)和本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 36 3 8 076 538049 A7 B7 五、發明説明（37 ) (請先閱讀背面之注意事項再填寫本頁) nOCIF自濃度2 5 0ng/ml起連續倍數稀釋後各取100/i 1放入 96洞的微穴盤中。然後，再以含有10%胎牛血清的α -MEM培養基100/i 1來懸濁鼠骨髓細胞3X105個後播種在上述穴盤中，在5 %二氧化碩，3 7 °C， 1 0 0 %濕度條件下培養一星期。培養7日後，依照實施例2中所示方法使用酸性礎酸酯 _ 活性測定組劑（Acid Phosphatase, Leucocyte, 型錄號碼No. 387-A, Sigma公司製品）進行染色檢驗破骨細胞之形成，以酒石酸共存下的酸性磷酸酯酶活性陽性細胞之減少情形做為0CIF活性。酸性磷酸酯酶活性陽性細胞之減少率，乃將染色細胞之色素溶解，再測定其吸光度而計算之。質言之，在經固定和染色過的細胞的穴盤中，加入 100^ 1的0.1N氫氧化銷-二甲亞碾混合液（1:1)並充分振盪之。充分溶解色素後，使用微穴盤讀譜儀（免疫型讀譜儀 NJ-2000型，Interred公司製品）測定波長590ηιη處和對照波長4 9 0 η πι處的吸光度。又測定吸光度時，使用未添加維生素D 3的洞孔做為對照洞孔。結果以未添加0 C I F的洞孔的為值度光吸表於示果結其示表值率分百用再經濟部中央標準局員工消費合作社印製本紙張尺度適用中國國家標準（CNS ) Α4規格（210X297公釐） 37 3 8 0 7 6 538049 A7 B7 五、發明説明（3 8 ) 表5 鼠骨髄細朐条中以0 C I F抑制破骨細贿！形成倩形（維生素D3 ) 0C IF濃度 (n g / m 1 ) 250 125 6 3 3 1 16 0 rOC IF (E) 0 0 3 62 80 100 nOCIF 0 0 27 27 75 100 (請先閲讀背面之注意事項再填寫本頁) 和nOCIF同樣地在rOCIF(E)上，在16ng/ml以上濃度時能看到隨量成正比率的破骨細胞形成抑制活性。 ii)基質細胞和鼠脾臓細胞的共同培養条中由維生素D3所誘導的破骨細胞形成之抑制依照宇田川等人的方法（參考Endocrinology, 125卷， 1805-181 3頁，1989年）進行由維生素D3所誘導基質細胞和鼠脾臓細胞之共同培養条中的破骨細胞形成試驗。即放入以含有2Χ1(Τ8Μ活性維生素D3, 2X1(T7M地塞米松（經濟部中央標準局員工消費合作社印製、 Explanation of the invention (3 6) (Please read the precautions on the back before filling out this page) The stomach _ test has obtained about 60 k D and about 120 k D 0 C I F bands. Therefore, __min 30 ~ 38 was refined and used as the origin of CHO cells to recombine OCIF [rOCIF (e}] fraction. Using BSA as the standard by the Raleigh method for protein quantification, it was confirmed that 1 obtained a concentration of 113 / ig / ml rOCIF (C) 4.5rol [Boshi Example 15] Analysis of N-terminal 耩诰 of Recombinant 0 CTF Refined 3 / ig rOCIF (E) and rOCIF (C) were fixed with Prospin (Perkin-Eiffle "product") After washing on a polyvinylidene fluoride (PVDF) membrane with 20% methanol, a protein sequence analyzer (patent specification 49 type 2, manufactured by Perkin-Elmer) was used to perform terminal amino acid sequence analysis. The results are shown in sequence number 7. The N-terminal amino acids printed by rOCIF (E) and rOCIF (C) printed by the Employees' Cooperatives of the Central Bureau of Standards, Ministry of Economic Affairs are the amino acids described in sequence number 5 The 22nd Glu from the start of sequence translation Met, 21 amino acids from Met to G 1 η are known as S igna 1 peptide. In addition, it was purified from IMR-90 culture medium The N-terminal amino acid sequence of natural OCIF cannot be analyzed, and it is presumed that the pseudo N-terminal G 1 is in culture or refined It may be converted to Pyroglutanric acid in the course of the process. [Example 16] Heavy-type (r) (1 CTF and diurnal (η)) (1 CIF biological life-i) in rats Inhibition of osteoclast formation induced by vitamin Ds in epiphyseal cell strips, α-MEM medium containing 2 X 1 0-8 M activated vitamin D 3 and 10% fetal bovine serum (made by Jebel BRL), Apply the refined rOCIF (E) and this paper size to the Chinese National Standard (CNS) A4 specification (210X297 mm) 36 3 8 076 538049 A7 B7 V. Description of the invention (37) (Please read the precautions on the back before filling in this (Page) nOCIF is continuously diluted from a concentration of 250 ng / ml to 100 / i 1 each and then placed in a 96-well micro-cavity tray. Then, an α-MEM medium containing 10% fetal bovine serum is added to 100 / i 1 3X105 murine bone marrow cells were suspended and seeded in the above tray, and cultured for one week at 5% SO2, 37 ° C, 100% humidity. After 7 days of culture, the results were as shown in Example 2. Methods An acidic basic acid ester _ activity test group (Acid Phosphatase, Leucocyte, Catalog No. 387-A, manufactured by Sigma) ) For forming the cells were stained test osteoclasts to reduce activity in the case of acid phosphatase-positive cells in the coexistence of the tartaric acid as 0CIF activity. The reduction rate of acid phosphatase-positive cells was calculated by dissolving the pigment in the stained cells and measuring their absorbance. In other words, 100 ^ 1 of a 0.1N hydroxide pin-dimethylimine mixed solution (1: 1) was added to the plate of the fixed and stained cells and thoroughly shaken. After the pigment was sufficiently dissolved, the absorbance at a wavelength of 590 nm and a control wavelength of 490 nm was measured using a micro-plate reader (immuno-spectrometer NJ-2000, manufactured by Interred). When the absorbance was measured, a hole without vitamin D 3 was used as a control hole. Results The photometric meter with a hole without 0 CIF as the value is shown in the table. The value shown in the table is 100%. The paper is printed by the China National Standards (CNS) Α4. Specifications (210X297 mm) 37 3 8 0 7 6 538049 A7 B7 V. Description of the invention (3 8) Table 5 In the rat bone ridge thin purlin, 0 CIF is used to suppress osteoclasty bribes! Formed in a clear shape (vitamin D3) 0C IF concentration (ng / m1) 250 125 6 3 3 1 16 0 rOC IF (E) 0 0 3 62 80 100 nOCIF 0 0 27 27 75 100 (Please read the precautions on the back first (Fill in this page again) As with nOCIF, rOCIF (E) shows an inhibitory activity on osteoclast formation at a concentration above 16ng / ml. ii) Inhibition of osteoclast formation induced by vitamin D3 in co-culture strips of stromal cells and murine splenocytes. Vitamins were induced by vitamin D3 in accordance with the method of Udagawa et al. (Ref. Endocrinology, Vol. 125, 1805-181 p. 3, 1989). Osteoclast formation test in co-culture strips of stromal cells and murine splenocytes induced by D3. That is, it is put in a print containing 2 × 1 (T8M active vitamin D3, 2X1 (T7M dexamethasone (Central Bureau of Standards, Ministry of Economic Affairs, Employee Consumer Cooperative)

Dexamethasone)以及10%胎牛血清的ex -MEM培養基（吉勿可BRL公司製品）連續稀釋的精製rOCIF(E), rOCIF(C),以及nOCIFlOOiul於96洞微穴盤中，再將鼠骨髓由來的基質細胞株ST2細胞（理研細胞資源庫-RCB0224)5x 103個與生後約8週齡的ddy鼠脾臓細胞lx 105個懸濁在含有10 %胎牛血清的α - Μ E Μ培養基1 0 0 μ 1中，然後播種在上述穴盤中 ,於5 %二氧化磺，3 7 °C， 1 0 0 %濕度條件下培養5日。培本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 38 3 8 0 7 6 538049 A7 B7 五、發明説明（3 9 ) 養5日後，用磷酸塩緩衝生理食塩水洗淨後，以乙醇/丙酮（1:1)溶液在室溫下固定細胞1分鐘，再用酸性磷酸酯酶活性測定組劑（Acid Phosphatase, Leucocyte,型錄號碼No.387-A， Sigma公司製品）染色撿驗破骨細胞形成情形。在酒石酸共存下酸性磷酸酯酶活性陽性細胞之減少情形做為0 C I F活性。另外，酸性磷酸酯_活性陽性細胞數的減少率按照實施例1 6 - i )項所記載方法，將所染色細胞的色素溶解而計算之。使用r 0 C I F ( E )和r 0 C I F ( C )試驗結果示於表6中，另外使用r 0 C I F ( E )和η 0 C I F試驗結果示於表7。表6 基質細胞和鼠脾臟細胞的共同培養条中用Π C T F抑 (請先閱讀背面之注意事項再填寫本頁) 經濟部中央標準局員工消費合作社印製制破骨細_形成情形 0C IF濃度 (n g / is 1 ) 50 25 13 6 0 rOC IF (E) 3 22 83 80 100 rOC IF (C) 13 19 70 96 100 本紙張尺度適用中國國家標準（CNS ) Α4規格（210X297公釐） 39 3 8 0 7 6 538049 A7 B7 五、發明説明（41 ) 號碼No. 387 -A， Sigma公司製品）染色檢驗破骨細胞之形成。以酒石酸共存下的酸性磷酯酶活性陽性細胞的減少做為 0CIF活性。又，酸性磷酸酯酶活性陽性細胞數的減少率按照實施例1 6 - i )項所記載方法，將染色細胞的色素溶解而計測之。其結果示於表8。寿8 鼠骨讁細朐条中用（1CTF抑制破骨細_形成情形( PTH ) 0 C I F濃度 (m g / m 1 ) 125 63 3 1 16 8 0 rOC IF (E) 6 58 58 53 88 100 n 0 C I F 18 47 53 56 91 100 (請先閱讀背面之注意事項再填寫本頁) 經濟部中央標準局員工消費合作社印製和c 0 C I F同樣，r 0 C I F ( E )中1 6 n g / η) 1以上濃度能看到隨容量成正比率的破骨細胞形成抑制活性。 1 v )由I L - U所誘導破骨細胞形成之抑制按照田村等人之方法（參考p r 〇 c · N a t 1 A c a d · S c i · U S A , 9 0 卷，]1 9 2 4 - 1 1 9 2 8 頁，1 9 9 3 年）進行由 I L _ 1 1 所誘導破骨細胞形成之試驗。卽在9 6洞孔徼穴盤中放入以含有 2 0 n g / m 1 I L - 1 ]以及1 0 %胎牛血清的α - Μ E Μ培養基（吉勿可 BRL公司製品）所稀釋的nOCIF以及精製rOCIF(E)10〇u 1。再於該洞孔穴盤中，將鼠新生兒頭蓋骨由來的前脂肪細胞株MC3T3-G2/PA6細胞（理研細胞種源庫RC81127)5X 103値本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 41 3 8 0 7 6 538049 A7Dexamethasone) and 10% fetal bovine serum in ex-MEM medium (made by Jebel BRL) serially diluted refined rOCIF (E), rOCIF (C), and nOCIF100iul in 96-well micro-cavity disks, and the rat bone marrow was derived Stromal cell line ST2 cells (Ricoh Cell Resource Bank-RCB0224) 5x 103 and ddy mouse spleen cells of about 8 weeks of age lx 105 suspended in α-M E Μ medium containing 10% fetal bovine serum 1 0 0 μ1, then seeded in the above tray, and cultured for 5 days at 5% sulphur dioxide, 37 ° C, 100% humidity. The paper size of the paper is in accordance with the Chinese National Standard (CNS) A4 (210X297 mm) 38 3 8 0 7 6 538049 A7 B7 V. Description of the invention (3 9) After 5 days of cultivation, it is washed with phosphoric acid buffered physiological food water Cells were fixed with ethanol / acetone (1: 1) solution at room temperature for 1 minute, and then stained with an acid phosphatase activity assay (Acid Phosphatase, Leucocyte, catalog number No.387-A, manufactured by Sigma). Test osteoclast formation. The decrease in acid phosphatase-positive cells in the presence of tartaric acid was defined as 0 C I F activity. In addition, the reduction rate of the number of acidic phosphate ester-active positive cells was calculated by dissolving the pigment of the stained cells according to the method described in Example 16-i). The test results using r 0 C I F (E) and r 0 C I F (C) are shown in Table 6, and the test results using r 0 C I F (E) and η 0 C I F are shown in Table 7. Table 6 Π CTF inhibitors used in co-culture strips of stromal cells and mouse spleen cells (please read the precautions on the back before filling this page) Printed osteoclasts by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs_Formation 0C IF concentration (ng / is 1) 50 25 13 6 0 rOC IF (E) 3 22 83 80 100 rOC IF (C) 13 19 70 96 100 This paper size applies the Chinese National Standard (CNS) Α4 size (210X297 mm) 39 3 8 0 7 6 538049 A7 B7 V. Description of the Invention (41) No. 387-A (manufactured by Sigma) Staining was used to examine the formation of osteoclasts. The decrease in acid phosphatase-positive cells in the presence of tartaric acid was taken as the 0CIF activity. The decrease rate of the number of cells with positive acid phosphatase activity was measured by dissolving the pigment in the stained cells by the method described in Example 16-i). The results are shown in Table 8. Shou 8 (1CTF inhibits osteoclast formation (PTH) 0 CIF concentration (mg / m 1) in rat bone calluses 125 63 3 1 16 8 0 rOC IF (E) 6 58 58 53 88 100 n 0 CIF 18 47 53 56 91 100 (Please read the notes on the back before filling out this page) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs Same as c 0 CIF, r 0 CIF (E) 16 ng / η) At concentrations above 1, osteoclast formation inhibitory activity can be seen in proportion to the volume. 1 v) Inhibition of osteoclast formation induced by IL-U was according to the method of Tamura et al. (Refer to pr oc · N at 1 A cad · S ci · USA, Vol. 90,] 1 9 2 4-1 1 Pp. 928, 193 years) to perform an osteoclast formation test induced by IL_11.放入 Place nOCIF diluted in 96-hole 徼 trays with α-Μ E Μ medium (20 ng / m 1 IL-1) and 10% fetal bovine serum (made by Jebel BRL). And refined rOCIF (E) 100u 1. In this hole plate, pre-adipocyte MC3T3-G2 / PA6 cells (RIKEN cell source bank RC81127) 5X 103 derived from the cranium of the neonatal rat were used. This paper is in accordance with the Chinese National Standard (CNS) A4 specification (210X297). Mm) 41 3 8 0 7 6 538049 A7

7 B 五、發明説明（42 ) 和生後約8星期的ddy鼠的脾臓細胞lx 105個，用IOOa/1 的含有%胎牛血清a -MEM培養基懸濁後播種，在5%的二氧化碳，3 7它，1 0 0 %的濕度下培養5日。培養5日後用磷酸塩緩衝生理食塩水洗淨後，再用乙醇/丙國（1 : 1 )溶液在室溫下固定細胞一分鐘，然後使用酸性磷酸酯酶活性測定組劑（Acid Phosphatase, Leucocyte,型錄號碼 No. 3 8 7 - A , S i g m a公司製品）染色檢驗破骨細胞形成。以酒石酸共存下計測酸性磷酸酯_活性陽性細胞數，以其減少情形做為0 C I P活性。其結果示於表9中。表9 由1丨，-：1丨所_漢#洒石酸共存下的酸件磯___活件腸件細_數 (請先閲讀背面之注意事項再填寫本頁) 0C IF濃度 5 0 0 1 2 5 31 7.8 2.0 0.5 (n g / m 1 ) nOCIF 0 0 14 13 49 31 rOCIF(E) 0 0 1 3 1 0 3 7 31 經濟部中央標準局員工消費合作社印製由上表中可知nOCIF和rOCIP(E)都在2ng/ml以上濃度能看到由I L - 1 1所誘導的破骨細胞形成的抑制活性和容量成正比率相關性。桉照上述使用各種標的細胞所進行破骨細胞形成有關試驗条中，可知顯示0 C I F抑制破骨細胞形成之結果，和維生素D3, PTH以及IL-11等破骨細胞形成誘導因子所誘導破本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 42 3 8 0 7 6 538049 A7 經濟部中央標準局員工消費合作社印製 B7 五、發明説明（43 ) 骨細胞之形成，幾乎以同樣濃度加以抑制功能。所以0 C I F 可以提供上述各種骨質趿收促進物質所誘導各種不同種類的骨量減少症的治療上有效應用之可行性。 [實施例1 7 ] 屋體塑和二（聚）體型0 C I F試料之調製分別含有1 0 0 a g r 0 C I F ( E )和r 0 C I F ( C )試料中，加入 1/1. 00容量的25%三氟乙酸後，再用以含有0.1 %三氟乙酸的3〇%乙腈平衡過的逆相分離管（？广(^0]、-1^,2.〇><25〇111111 ,YMC公司製品）處理，用在50分鐘内能成為55 %濃度的乙腈直線梯度溶液，以每分鐘0.2 ml的流速溶洗，而級分各 0 C I F的尖峰餾分。所得尖峰餾分經凍結乾燥而分別得到單體型0 C I F和二（聚）體型0 C I F。 [實施例1 8 ] 重紐塑0 C I F夕分芊景測宏按照實施例3 - v i )項所示方法，使用逆相分離管精製的單體型和二（聚）體型η 0 C I F，以及用實施例1 7所記載方法所精製的單體型的二（聚）體型r 0 C I F約含1 u g的試料以減壓濃縮之。就上述試料依照實施例4中所示方法，進行 S D S處理，S I) S -聚丙烯醯胺電泳以及銀染色。非還原條件下和還原條件下所進行電泳結果分別示於第6圖和第7 _ Ο 其結果，在非還原條件下，任何單體型試料皆檢驗有 60kD的蛋白質帶之存在，另外，在任何二（聚）體型試料中 ,撿驗有120k D的蛋白質帶存在。另外，在還原條件下， 43 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 3 8 0 7 6 (請先閱讀背面之注意事項再填寫本頁) 538049 A7 B7 經濟部中央標準局員工消費合作社印製五、發明説明（44 ) 任何試料僅檢驗得約6 0 k D的蛋白質帶存在。因此，I M R - 9 0 細胞由來之nOCIF, 293/ΕΒΝΑ細胞由來之重組型OCIF,以及CH0細胞由來之重組型0CIF之各個單體型和二（聚）體型大致顯示相同分子量C [實施例1 9 ] ΙΟ·90細朐由夾天然型0CI"D重塑0CTF的N_結合型耱鐽„之_„支|_.息_分-王^量_之...m— 含據實施例3 - v i )項所示方法，使用逆相分離管精製成的單體型和二（聚）體型η 0 C I F ,以及按照實施例1 7中所記載方法精製成的單體型和二（聚）體型r 0 C I F的各個試料約5/ig加以減壓濃縮，再加入lOOmM 2 -頸基乙醇的50mM磷酸塩緩衝液（P Η 8 . 6 ) 9 , 5以1於上述試料並溶解之，再加入 0 . 5 /i ]的2 5 0 11/«|1濃度的1^聚__溶液（生化學工業公司製品），在3 7 C下放置一日。這些試料中，再加入含2 m Μ EDTA, 5%SDS,以及 0.02% 溴化酚藍的 20mM Tris-Hcl( Ρ Η 8 , 0 ) 1 0 w 1 ,在1 0 0 C下加熱5分鐘。取上述試料之1 w 1 ，按照實施例4所示方法進行SDS -聚丙烯醯胺電泳後，再施以銀染色。其結果示於第8圖中。結果，經N -聚隨_處理而去除N -結合糖鏈的0CIF蛋白質，在還原條件下的分子量皆示約40kD。未進行耱鏈去除處理的IMR-90細胞由來之nOCIF, 293/EBNA細胞由來之 rOCIF,以及CH0細胞由來之rOCIF各在還原條件下的分子量皆為約60kD,因此，可知這些0CIF偽在其分子内含有N-結合糖鐽的糖蛋白質。 1! ----φ II (請先閱讀背面之注意事項再填寫本頁)7 B V. Description of the invention (42) and spleen cells of 105 ddy rats about 8 weeks after birth, 105 spleen cells were suspended in 100% a fetal bovine serum a-MEM medium containing 100a / 1 and seeded, suspended in 5% carbon dioxide, 3 7 it was cultured at 100% humidity for 5 days. After 5 days of culture, the cells were washed with phosphate buffered saline and then washed with ethanol / C (1: 1) solution at room temperature for one minute, and then the acid phosphatase activity assay group (Acid Phosphatase, Leucocyte) was used. (Catalog No. 3 8 7-A, Sigma Co., Ltd.) staining to check osteoclast formation. The number of acid phosphate-activation-positive cells was measured in the presence of tartaric acid, and the decrease was regarded as 0 C I P activity. The results are shown in Table 9. Table 9 From 1 丨,-: 1 丨所 _ 汉 # The acid pieces in the coexistence of sprinkled acid ___ the number of live intestinal pieces (please read the precautions on the back before filling this page) 0C IF concentration 5 0 0 1 2 5 31 7.8 2.0 0.5 (ng / m 1) nOCIF 0 0 14 13 49 31 rOCIF (E) 0 0 1 3 1 0 3 7 31 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs. Both nOCIF and rOCIP (E) showed a positive correlation between the inhibitory activity and capacity of osteoclast formation induced by IL-1 at concentrations above 2ng / ml. In the test strips related to osteoclast formation using various target cells as described above, it can be seen that the results of 0 CIF inhibit osteoclast formation, and the damage induced by osteoclast formation inducing factors such as vitamin D3, PTH and IL-11. Paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) 42 3 8 0 7 6 538049 A7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs B7 5. Invention Description (43) The formation of bone cells is almost the same Concentration to suppress the function. Therefore, 0 C I F can provide the feasibility of effective application in the treatment of various types of osteopenia induced by the above-mentioned various osteogenesis-promoting substances. [Example 1 7] The preparation of the house plastic and two (poly) 0 CIF samples contains 1 0 agr 0 CIF (E) and r 0 CIF (C) samples, respectively, adding 1/1. 00 capacity of 25 % Trifluoroacetic acid, and then equilibrated with 30% acetonitrile containing 0.1% trifluoroacetic acid in a reversed phase separation tube (? ((0), -1, 2, 2.0) < 25〇111111, YMC Co., Ltd.) treatment, using a linear gradient solution of acetonitrile that can become 55% concentration within 50 minutes, dissolving at a flow rate of 0.2 ml per minute, and each fraction of 0 CIF spike fractions. The resulting spike fractions were freeze-dried and separately The haplotype 0 CIF and the di (poly) body 0 CIF were obtained. [Example 1 8] Remodeling 0 CIF Evening Vision Macro According to the method shown in Example 3-vi), using a reverse phase separation tube purification The haplotype and di (poly) form η 0 CIF, and the haplotype di (poly) form r 0 CIF refined by the method described in Example 17 contained about 1 ug of the sample and concentrated under reduced pressure. For the above sample, S D S treatment, SI) S-polyacrylamide electrophoresis, and silver staining were performed according to the method shown in Example 4. The results of electrophoresis performed under non-reducing conditions and reducing conditions are shown in Figure 6 and 7 _ 0. As a result, under non-reducing conditions, any haplotype samples were tested for the presence of 60kD protein bands. In addition, in In any di (poly) -type sample, 120k D protein bands were detected. In addition, under the reducing conditions, 43 paper sizes are applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm) 3 8 0 7 6 (Please read the precautions on the back before filling this page) 538049 A7 B7 Central Standard of the Ministry of Economic Affairs Printed by the Bureau's Consumer Cooperatives V. Description of Invention (44) Any sample only detected about 60 kD of protein bands. Therefore, the respective haplotypes and di (poly) types of nOCIF from IMR-9 0 cells, recombinant OCIF from 293 / ΕΒΝΑ cells, and recombinant 0CIF from CH0 cells showed approximately the same molecular weight C [Example 1 9 ] ΙΟ · 90 Fine 朐 N-combined type of 0CTF is reshaped by sandwiching the natural type 0CI " D to reshape the N_combined type 耱鐽 of the branch | _. 息 _ 分-王 ^ 量 _ 的 ... m — Including Example 3 -The method shown in item vi) uses a haplotype and a di (poly) body type η 0 CIF refined from a reverse phase separation tube, and a haplotype and a di (poly) body refined according to the method described in Example 17 Each sample of size r 0 CIF was concentrated under reduced pressure at about 5 / ig, and 100 mM 2-necked ethanol in 50 mM phosphonium phosphate buffer solution (P Η 8.6) 9, 5 was added to the above sample and dissolved, and then Add 0.5% / i] 2 5 0 11 / «| 1 concentration of 1 ^ poly__ solution (product of Biochemical Industry Co., Ltd.), and leave it at 37 ° C for one day. To these samples, 20 mM Tris-Hcl (P 8, 0) 10 w 1 containing 2 μM EDTA, 5% SDS, and 0.02% brominated phenol blue was added, and heated at 100 C for 5 minutes. 1 w 1 of the above sample was taken, followed by SDS-polyacrylamide electrophoresis according to the method shown in Example 4, and then subjected to silver staining. The results are shown in Fig. 8. As a result, the OCIF protein that had been removed by N-poly and N-binding sugar chains showed molecular weights of about 40 kD under reducing conditions. The molecular weights of nOCIF derived from IMR-90 cells, rOCIF derived from 293 / EBNA cells, and rOCIF derived from CH0 cells were all about 60kD under reducing conditions without the removal of 耱 chain. Contains glycoproteins of N-bound glycogen. 1! ---- φ II (Please read the precautions on the back before filling this page)

、1T 本紙張尺度適用中國國家標準（CNS ) Α4規格（210X297公釐） 44 3 8 0 7 6 538049 A7 B7 經濟部中央標準局員工消費合作社印製五、發明説明（45 ) 1 1 [實施例2 0 ] 1 | 0C IF (類緣物）〇 Π N A ^紳备增51 以及塩甚序列夕決定 1 按昭實施例 1 0和 1 1中所示，經約化過的若干陽性噬菌諸 1 1 體中先 1 之 —^ > 獲得在 pBKCMV(Stratag ene公司製品）插入有閱讀 1 0C IF cDN A 的質粒 p B K 0 C I F的轉化株，同時，從其他若干陽背之 1 1 I 性噬菌體也能得到插入有不同長度的插入體的質粒的轉化注意事 1 1 株 0 增殖具有這些質粒的轉化株，再依據常法精製質粒。項再 1 Φ | 利用 Ta q二去氧終端循環定序組劑（Perk in -Elmer 公司製品 ▲ 寫本頁 )決定上述插入物DNA的塩基序列。所使用引物乃依據 T3 . 1 I Τ7引物 (S t r at a g e η e公司製品）以及 0C IF cDN A的塩基序列設 1 1 I 計而成的合成引物 0 原始型態的0 C IF以外 ,0C IF 類緣物金 1 I 訂部有 4 種 (0C IF2 3 , 4，5 )存在。所決定的 0C IF2cDNA的 1 塩基序列示於序列 m 碼8,從該序列推定的胺基酸序列示 1 1 於序列 Wt 碼 9。所決定的〇CIF3cDNA的塩基序列示於序列號 1 | 碼 10 t 由該序列推定的胺基酸序列示於序列號碼 1 1 〇所決 1 •f 定的 0C IF4c DN A的塩基序列示於序列號碼1 2 ,由該序列推定的胺基酸序列示於序列號碼1 3。所決定的 0CIF5cDNA的 1 1 塩基序列示於序列號碼1 4，由该序列推定的胺基酸序列示 1 1 於序列 m 碼 15 〇這些 0C IF類緣物的構造特徵示於第9- -12 1 I 圖簡 αο 早說明如下 0 1 I 1 QI ：TF2 1 1 I 0C ：IF | c D N A 的塩基序列（參照序列號碼6 )的第2 6 5個的鳥 1 1 嘌昤到第 285個的鳥嘌昤有21bp的缺失，胺基酸序列而言， 1 1 0 C I F 的胺基酸序列 (參照序列號碼5 )的第68個的谷胺酸（簡 1 1 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 45 3 807 6 538049 A7 ______ B7 五、發明説明（46 ) 稱G 1 u )到第7 4個的谷胺酸（G 1 u )的7個胺基酸有缺失。、 1T This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) 44 3 8 0 7 6 538049 A7 B7 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (45) 1 1 [Example 2 0] 1 | 0C IF (family-like objects) 〇 NA NA ^ Shen Bei Zeng 51 and the sequence decision 1 As shown in Example 1 0 and 11, several positive phages have been reduced. 1 1 of the first 1 — ^ > A transformant obtained by inserting a plasmid p BK 0 CIF that reads 1 0C IF cDN A into pBKCMV (manufactured by Stratagene) was obtained from several other positive 1 1 I genes. Transformation of plasmids with inserts of inserts of different lengths can also be obtained from phages. 11 Strains 0 The transformants with these plasmids are propagated, and the plasmids are purified according to the usual method. Item Re 1 Φ | Ta q dideoxy terminal cycling sequencing kit (Perk in-Elmer Corporation ▲ write this page) is used to determine the fluorenyl sequence of the insert DNA. The primers used are synthetic primers based on T3. 1 I T7 primers (S tr at age η company) and 0C IF cDN A. The primers are based on 1 1 I. In addition to 0 C IF in the original form, 0 C There are 4 types of IF-type fate gold 1 I order (0C IF2 3, 4, 5). The 1 塩 motif sequence of the determined 0C IF2 cDNA is shown in sequence m code 8, and the amino acid sequence deduced from this sequence is shown in sequence 1 1 in sequence Wt code 9. The determined fluorenyl sequence of 〇CIF3cDNA is shown in SEQ ID NO: 1 | Code 10 t The amino acid sequence deduced from this sequence is shown in SEQ ID NO: 1 1 〇 determined 1 • f determined OC of IF4c DN A is shown in the sequence Number 1 2 and the amino acid sequence deduced from this sequence is shown in SEQ ID NO: 1 3. The determined 1 1 amino acid sequence of the 0CIF5 cDNA is shown in SEQ ID NO: 14 and the amino acid sequence deduced from this sequence is shown in 1 1 in the sequence m code 15 〇 The structural characteristics of these 0C IF-type margins are shown in sections 9-12 1 I abbreviation αο Early explanation is as follows: 0 1 I 1 QI: TF2 1 1 I 0C: IF | Guanine has a 21bp deletion. As for the amino acid sequence, the 68th glutamic acid of the amino acid sequence of 1 10 CIF (refer to sequence number 5) (Simplified 1 1 This paper size applies to Chinese national standards ( CNS) A4 specification (210X297 mm) 45 3 807 6 538049 A7 ______ B7 V. Description of the invention (46) It is called G 1 u) to the 7th glutamic acid (G 1 u). Is missing.

0LILLFX (請先閱讀背面之注意事項再填寫本頁) 0 C I F c D N A的塩基序列（參照序列號碼6 )的第9個的胞嘧啶核管（簡稱C y d )變成鳥嘌昤，就胺基酸序列而言， 0 C I P的胺基酸序列（參照序列號碼5 )的第1 9個的天冬醯胺（簡稱A s η )變成賴胺酸（簡稱L y s )。但此乃指訊息序列中的胺基酸取代情形，所分泌出來的〇 C I F 3可能不會受影響。 OCIFcDNA的塩基序列（參照序列號碼6)的第872個的鳥嘌昤到第989個鳥嘌昤，有U7bP的缺失，就胺基酸序列而言，〇C IF的胺基酸序列（參照序列號碼5)的第27 0個的蘇胺酸（簡稱T h r )到第3 0 8個的白胺酸（簡稱L e tr)至有3 9個胺基酸缺失。 0JUF4 經濟部中央標準局員工消費合作社印製 OCIFcDNA的塩基序列（參照序列號碼6 )的第9個胞嘧啶核酸（簡稱C y d )變成鳥嘌昤，就胺基酸序列而言，0 c 1 F 的胺基酸序列（參考序列號碼5 )的第1 9個的天冬醒胺（簡稱 A s η )變成賴胺酸（簡稱L y s )。又，第2 2個的鳥_ _變成胸腺核苷（簡稱T ),就胺基酸序列而言，〇 c 1 p的胺基酸序列（參照序列號碼5)的第14個的丙胺酸（簡稱A]a)變成絲胺酸（簡稱S e r )。但是此乃訊息序列中的胺基酸取代而已，所分泌的0 C I F 4可能不受影響。 OCIFcDNA的塩基序列（參照序列號碼6)的第400個和第 4 0 1個之間約有4 k b的插人序列2 Π n t r ο n e 2 )之插人，轉錄密碼譯讀架構止於其中。胺基酸序列而言，0 c 1 F的胺基酸本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 46 3 807 6 538049 Α7 __ Β7 五、發明説明（47 ) 序列（參照序列號碼5 )的第1 1 2値的丙胺酸（簡稱A 1 a )之後 Ρίί加上由2〗個胺基酸所構成的新穎的胺基酸序列。 OClFcDNA的塩基序列（參考序列號碼6)的第9個的胞 _啶核酸變成鳥嘌昤，就胺基酸序列而言，0 C I F的胺基酸序列（參照序列號碼5 )的第1 9個的天冬醯胺（簡稱A s η )變成賴胺酸（簡稱L y s )。但是此乃訊息序列中的胺基酸取代，戸厅分泌的0 C I F 5可能不受其影響。 OClFcDNA的塩基序列（參照序列號碼6)的第400個和第 4〇1個之間插入有約1 . 8kb的插入序列2的後半部分，轉錄密碼譯讀架構止於其中。就胺基酸序列而言，0CIF的胺基酸序列（參照序列號碼5 )的第1 1 2個的丙胺酸（A 1 a )後面附加有由12個胺基酸所構成的新穎胺基酸序列。 [實施例2 1 ] Q C I F類綠物（V a ν· a u t )之生産— LI_0CIF·綠物現醫粒的調製經濟部中央標準局員工消費合作社印製實施例2 0中所得0 C I F類緣物c D Ν Α中，分別插入有 0CIF2及 3 的 cDNA而成質粒，PBK0CIF2, PBK0CIF3,以限制酶Xhol以及BamHI (寶酒造公司製品）消化，切割得0CIF2 和3之c D N A ,利用瓊脂糖電泳分離後，利用Q I A E Z凝_萃取組劑（吉阿研公司製品）精製之。上述0CIF2和3的cDNA 使用連接組劑V e r . 2 (寶酒造公司製品）插入在事前利用限制酶X h ο I和B a πι Η I (寶酒造公司製品）消化過的表現質粒 P C Ε Ρ 4 ( I n u i t r 〇 g e n e公司製品），藉此進行大腸_ D Η 5 σ (吉本紙張尺度適用中國國家標準（CNS ) Α4規格（210Χ297公釐） 3 8 0 7 6 (請先閱讀背面之注意事項再填寫本頁) 47 538049 A7 __ B7 五、發明説明（48) %可B RL公司製品）之轉化。又實施例20中所得OCIF類緣物cDNA中，插人有0CIF4 的cDNA的質粒PBK0CIF4以限制_ Spel和Xhol (寶酒造公司製品）消化，再用瓊脂糖電泳法分離後，使用Q I A E Z凝膠萃 ®組_ (吉阿研公司製品）精製之c這些oc ϊΡ4的cDNA彳吏用連接用組劑V e r 2 (寶酒造公司製品）插入在事前用限_ _ N h e I和Z h ο I (寶酒造公司製品）消化好的表現質粒P C E P 4 ( I n v i t r 〇 g e n e公司製品），而進行大腸_ D Η 5 ex (吉勿可B R L 公司製品）之轉化。經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) 又，實施例20中所得0CIP類緣物cDNA中，插入有〇〇1?5的（^“的質粒981(0(：：^5以限制_}|丨以111(寶酒造公司製品）消化，切割得0 C I F 5 c D N A的密碼領域之5 ’領域，用瓊脂糖電泳法分離後，使用Q I A E Z凝膠萃取組劑（吉阿研公司製品）精製之。實施例1 3 - i )項中所得0 C I F表現質粒 PCEP0CIF用限制睛Hindlll (寶酒造公司製品）消化，去除 0 C I F c D N A的密碼領域之5 ’領域，含有p C E P質粒和0 C 1 F c D N A 的3’領域的DNA片段pCEPOCIF-3’以瓊脂糖電泳法分離後，使用（31八£乂凝_萃取組劑（吉阿研公司製品）精製之。使用連接用組劑Ver.2(寶酒造公司製品）將上述0CIF5cDNA的 Hindlll片段插人在pCEPOCIP-3’上，進行大腸_DH5a (吉勿可B R L公司製品）之轉化。增殖所得轉化株，使用吉阿研分離管（吉阿研公司製品）精製捅入有0CIF2, 3, 4， 5的cDNA的表現質粒 p C E P 0 C I P 2， 3， 4 , 5。使用乙醇使0 C I P類緣物表現質粒沈本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 48 3 8 07 6 538049 Α7 Β7 五、發明説明（49 ) ^後，溶解在無鋪麵餾水中以供下述操作用途。 IF類錄物oDNA的钜塹袠琨迦其活桦：> 制宙用實施例2卜i )項中所得〇 C I F類緣物表現質粒 P c E P 0 C I F 2 , 3，4 , 5 ,按照實施例1 3 - i i )項中所述方法使 0CIF類緣物做短暫地表現，並調査其活性。結果這些 0 C I F類緣物確認有微弱活性。 [實施例2 2 ] QX IF變思體製作經濟部中央標準局員工消費合作社印製 (請先閲讀背面之注意事項再填寫本頁) 11_ϋΧ IF戀里體ρΠΝΑ僂代無件繁殖用質粒黼艚夕餺作 5以g的實施例1 1中所記載的質粒載體，用限制酶 BamHl和Zhol (寶酒造公司製品）切割。切割的DNA提供調製用瓊脂糖凝膠電泳處理。分離含有OCIFcDNA的全長約 1.6kb的DNAH段，使用QIAEZ凝膠萃取組劑（吉阿研公司製品）精製，而得溶解於無菌蒸餾水中的2 0 // 1 D N Μ容液（1 ) 。其次，將 3// g 的 pBluescript IISKMStratagene公司製品）用限制酶B a in Η I和Z h ο I (寶酒造公司製品）切割。切割得 DNA提供調製用瓊脂糖凝_電泳分離，分離得約3.0kb的 D H A Η段，再用Q I A E Z凝醪萃取組劑（吉阿研公司製品）精製，而獲得溶解在無_蒸餾水的2 0 α 1 D N A溶液（2 )。混合 ]μ 1的D N A溶液（2 )和4 y 1的D N A溶液（1 ),添加5 "]的D N A 連接用組劑V e r . 2 I液（寶酒造公司製品），混合後在1 6 °C下保溫30分鐘而進行連接反應。又，以後的連接反應皆以 16 υ下保溫3 0分鐘的條件下進行之。使用上述連接反應液，按照下述條件轉化大腸_。又本紙張尺度適用中國國家標準（CNS ) Α4規格（210Χ297公釐） 49 3 80 7 6 538049 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明（5〇 ) ，以後之大腸菌的轉化皆採用下述條件進行。將5m 1的連接反應液和100 β】的大腸_DH5or competent細胞（吉勿可 BRL公司製品）在15ml用無菌管中（岩城玻璃公司製品）混合，放置冰水中30分鐘。在42 °C保溫45秒鐘後，添加250/i 1 的L培養基（1%胰陳，0·5%酵母萃取物，1%氡化鈉）在 37°C攪拌培養之。在含有50"g/nil安比西林的2ml L洋菜培養基上展開50m 1的_液。在37¾下培養一夜，所& | 出來的6種麵落，在2nrl的L-安比西林液狀培養基中再：jg 養一夜，然後調査各_株所具有的質粒的構造。而_彳#& P B 1 u e s c r i p t I I S K + 的 B a m Η I，Z h ο I 切割部位插入含 0 C I F c D N A金長約1 , 6 k b的D H A Η段構造的質粒（以下，簡稱其為 PSK + -0C IP)。0LILLFX (Please read the precautions on the back before filling this page) 0 The 9th cytosine nuclear tube (referred to as C yd) of the cytidine sequence of CIF c DNA (refer to sequence number 6) becomes guanine. In terms of sequence, the 19th asparagine (referred to as A s η) of the amino acid sequence (refer to sequence number 5) of 0 CIP becomes lysine (referred to as Lys). However, this refers to the amino acid substitution in the message sequence, and the secreted 0 C I F 3 may not be affected. The 872th guanine to the 989th guanine of the OCIFcDNA (reference sequence number 6) has a deletion of U7bP. As for the amino acid sequence, the amino acid sequence of OC IF (reference sequence No. 5) from the 270 th threonine (referred to as T hr) to the 308 th leucine (referred to as Le tr) to 39 amino acid deletions. 0JUF4 The 9th cytosine nucleic acid (referred to as C yd) of the fluorene-based sequence (referred to as sequence number 6) of the OCIFcDNA printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs becomes guanine. As far as amino acid sequences are concerned, 0 c 1 F The asparagine (A s η) of the 19th amino acid sequence of the amino acid sequence (reference sequence number 5) is changed to lysine (L ys). In addition, the 22nd bird _ _ becomes thymidine (abbreviated as T). As for the amino acid sequence, the 14th alanine of the amino acid sequence of oc 1 p (refer to sequence number 5) ( Abbreviation A] a) becomes serine (abbreviated as Ser). However, this is just an amino acid substitution in the message sequence, and the secreted 0 C I F 4 may not be affected. OCIFcDNA has about 4 kb of intervening sequences 2 Π n t r ο n e 2) between the 400th and 401th sequences of the base sequence (reference sequence number 6) of OCIFcDNA. As for the amino acid sequence, the paper size of 0 c 1 F amino acid is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm) 46 3 807 6 538049 Α7 __ Β7 V. Description of the invention (47) Sequence (refer to SEQ ID NO: 5) is followed by the 1 12th alanine (referred to as A 1 a) followed by a novel amino acid sequence composed of 2 amino acids. The 9th cytosine nucleic acid of OClFcDNA (reference sequence number 6) becomes guanine. As far as the amino acid sequence is concerned, the 0th CIF amino acid sequence (reference sequence number 5) is the 19th Asparagine (abbreviated as A s η) into lysine (abbreviated as Lys). However, this is an amino acid substitution in the message sequence, and the 0 C I F 5 secreted by the pupal hall may not be affected by it. The second half of the 1.8-kb insertion sequence 2 was inserted between the 400th and the 401st of the fluorene-based sequence (reference sequence number 6) of the OClFcDNA. As for the amino acid sequence, the 12th alanine (A 1 a) of the amino acid sequence of 0CIF (refer to sequence number 5) is followed by a novel amino acid composed of 12 amino acids sequence. [Example 2 1] Production of QCIF green matter (V a ν · aut) — LI_0CIF · Modulation of current green medicine capsules Printed in Example 2 0 CIF type marginal matter obtained by employee consumer cooperative of Central Standard Bureau of Ministry of Economic Affairs In c D Ν Α, cDNAs of 0CIF2 and 3 were inserted into the plasmid, PBK0CIF2, PBK0CIF3, digested with restriction enzymes Xhol and BamHI (products of Takara Shuzo Co., Ltd.), c DNA of 0CIF2 and 3 were cut, and separated by agarose electrophoresis , Refined by QIAEZ coagulation_extracting agent (products of Ji'ayan Company). The above-mentioned cDNAs of 0CIF2 and 3 were inserted into the expression plasmid PC Ε Ρ 4 (prepared by Takara Shuzo Co., Ltd.) using restriction enzymes X h ο I and B a π Η I (Takara Shuzo Co., Ltd.) using the ligation reagent Ver. 2 (Takara Shuzo Co., Ltd.). I nuitr 〇gene products) to carry out large intestine _ D Η 5 σ (Yoshimoto paper size applies Chinese National Standard (CNS) Α4 specifications (210 × 297 mm) 3 8 0 7 6 (Please read the precautions on the back before filling (This page) 47 538049 A7 __ B7 V. Description of the invention (48)% can be produced by B RL Company). In the OCIF marginal cDNA obtained in Example 20, the plasmid PBK0CIF4 inserted with the cDNA of 0CIF4 was digested with restriction _ Spel and Xhol (produced by Takara Shuzo Co., Ltd.), and then separated by agarose electrophoresis, and then QIAEZ gel extraction was used. Group _ (products of Ji'a Research Co., Ltd.) refined oc ϊ ΡΡ4 cDNA ligating agent Ver er 2 (product of Takara Shuzo Co., Ltd.) is inserted in advance _ _ N he I and Z h ο I (Takara Shuzo Co., Ltd. (Product)) digested expression plasmid PCEP 4 (product of Invitrogene Inc.) and transformed large intestine _ D Η 5 ex (product of Jebel BRL). Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs (please read the precautions on the back before filling out this page). Also, the 0CIP-type marginal cDNA obtained in Example 20 was inserted with a plasmid of 0.001. 981 (0 (:: ^ 5 to limit _} | 丨 digested with 111 (product of Takara Shuzo Co., Ltd.), cut to 5 'field of 0 CIF 5 c DNA code field, separated by agarose electrophoresis, and used QIAEZ gel Extraction kit (product of Ji'an Research Co., Ltd.) was refined. The 0 CIF expression plasmid PCEP0CIF obtained in Example 1 3-i) was digested with Hindlll (manufactured by Takara Shuzo Co., Ltd.) to remove 0 CIF c DNA. Field, the 3 'field DNA fragment pCEPOCIF-3' containing the p CEP plasmid and 0 C 1 F c DNA was separated by agarose electrophoresis, and used (31 乂乂 coagulation_extraction group reagent (product of Ji'a Research Co., Ltd.) Refined. Using the ligation kit Ver.2 (product of Takara Shuzo Co., Ltd.), the Hindlll fragment of the above-mentioned 0CIF5cDNA was inserted into pCEPOCIP-3 ', and transformation of large intestine _DH5a (product of Jibeike BRL Co., Ltd.) was performed. , Using Ji'ayan separation tube (Products from Ji'an Research Co., Ltd.) Refined expression plasmids pCEP 0 CIP 2, 3, 4, 5 with cDNAs of 0CIF2, 3, 4, and 5. Use ethanol to make 0 CIP-like marginal expression plasmids. Chinese National Standard (CNS) A4 specification (210X 297 mm) 48 3 8 07 6 538049 A7 B7 V. Description of the invention (49) ^, dissolved in non-surfaced distilled water for the following operations. IF class recording DNAGaqi living birch of oDNA: > CIF-like marginal expression plasmid P c EP 0 CIF 2, 3, 4, 5 obtained in Example 2 (b) of the method used in the system, according to Example 1 3 -The method described in item ii) makes the 0CIF-type fate perform transiently, and investigates its activity. As a result, these 0 CIF-type fate were confirmed to have weak activity. [Example 2 2] QX IF transfiguration production center of the Ministry of Economic Affairs Printed by the Consumer Bureau of the Standards Bureau (please read the precautions on the back before filling out this page) 11_ Χ IF 恋里体 ρΠΝΑ 偻 Substitute the plasmid for the non-reproductive reproduction 黼艚 Xi 馎 5 5 g as described in Example 11 Plasmid vector, cut with restriction enzymes BamHl and Zhol (made by Takara Shuzo Co.). The cut DNA provided The preparation was processed by agarose gel electrophoresis. A DNAH segment of approximately 1.6kb in length containing OCIFcDNA was separated and purified using QIAEZ gel extraction kit (product of Giyaken Co., Ltd.) to obtain 2 0 // 1 dissolved in sterile distilled water. DN M container solution (1). Next, 3 // g of pBluescript II (manufactured by SKMStratagene) was cut with restriction enzymes Ba in Η I and Z h ο I (manufactured by Takara Shuzo Co., Ltd.). The cut DNA is provided for modulation by agarose gel electrophoresis, and the DHA segment of about 3.0 kb is separated, and then purified by QIAEZ gel segment extraction kit (product of Ji'ayan Corporation) to obtain 2 0 dissolved in non-distilled water. α 1 DNA solution (2). Mix] μ 1 DNA solution (2) and 4 y 1 DNA solution (1), add 5 "] DNA ligation reagent Ver. 2 I solution (product of Takara Shuzo), mix at 16 ° Incubation reaction was carried out by incubating at C for 30 minutes. In addition, the subsequent connection reactions were performed under the condition of incubation at 16 υ for 30 minutes. Using the above ligation reaction solution, large intestine was transformed under the following conditions. And this paper size applies the Chinese National Standard (CNS) A4 specification (210 × 297 mm) 49 3 80 7 6 538049 A7 B7 printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (50), subsequent transformation of coliform All were performed under the following conditions. 5 ml of the ligation reaction solution and 100 β] large intestine_DH5or competent cells (product of Jebelco BRL) were mixed in a 15 ml sterile tube (product of Iwaki Glass Co., Ltd.) and left in ice water for 30 minutes. After incubating at 42 ° C for 45 seconds, 250 / i 1 of L medium (1% pancreatic aging, 0.5% yeast extract, 1% sodium trioxide) was added and cultured at 37 ° C with stirring. 50ml of agar solution was developed on 2ml L agar culture medium containing 50 g / nil ampicillin. After cultured overnight at 37¾, the 6 kinds of noodles emerged, and then cultured in 2nrl L-ampicillin liquid medium: jg overnight, and then investigated the plasmid structure of each strain. A _ 彳 # & PB 1 uescript IISK + B am Η I, Z h ο I cutting site is inserted with a 0 CIF c DNA gold length of about 1, 6 kb DHA Η segment constructed plasmid (hereinafter, referred to as PSK + -0C IP).

ii) Cvs以SfirBV代的戀里體的餺作 (1 )瀵人變S 製作序列表中序列號碼4所記載的胺基酸序列中，g i 7 4 1 8 1 , 2 5 6 , 2 9 8和3 7 9個的C y s殘基以S e r殘基取代的變異龄。第174個Cys以Ser取代的變異體命名為OCIP-Cig^ g 181個Cys以Ser取代的變異體命名為0CIF-C20S,第256ftii) Cvs uses the SfirBV generation of the lyophilic body (1) 瀵人变 S to make the amino acid sequence described in sequence number 4 in the sequence table, gi 7 4 1 8 1, 2 5 6, 2 9 8 And 3,79 Cys residues were replaced by Ser residues. The 174th Cys Ser-substituted variant is named OCIP-Cig ^ g The 181th Cys Ser-substituted variant is named 0CIF-C20S, 256ft

Cys以Ser取代的變異體命名為0CIF-C21S,第298海ir , M L y S 以 S e r取代的變異體命名為0 C I F - C 2 2 S。第3 7 9値c y s以s e P驭代的變異體命名為0CIF-C23S。為製作變異體，首先# # Cys殘基的編碼塩基序列以Ser殘基的編碼塩基序列代之。變異的導入藉兩階段的P C R (聚合酶鏈反應）而_ g 。以後皆稱為一階段PCR反應。第一階段由兩個 (請先閱讀背面之注意事項再填寫本頁〕 -訂 dThe Cys variant with the Ser substitution was named 0CIF-C21S, the 298th ir, and the M L y S variant with the Se substitution was named 0 C I F-C 2 2 S. The 3 7 9 値 c y s was named 0CIF-C23S after the mutant of s e P. To make a variant, first the ## Cys residue coding sequence is replaced by the Ser residue coding sequence. The introduction of mutations was achieved by two-phase PCR (polymerase chain reaction) and g. Hereinafter referred to as a one-stage PCR reaction. The first stage consists of two (please read the notes on the back before filling this page)-order d

3 8 0 7 6 538049 A7 B7五、發明説明（5!) P C R 1和P C R 2 )所構成。 P C R 1 g應液 1 0 X E X T a q緩衝液（寶酒造公司） 2.5mM dNTP 溶液實施例1 1所記載質粒載體（8 n g / m 1 ) 無菌蒸餾水 2 0 /i Μ引物1 100 u Μ引物2 (導入變異用） Ex Ta<i(寶酒造公司） PCR2g騰液 10X Ex Taq緩衝液（賫酒造公司） 2 . 5 m M d N T P 溶液實施例11記載之質粒載體（8ng/ml) 無菌蒸餾水 2 0 w Μ弓I物3 10^1 u 73 . u 10 u u 73.5α 1 u (請先閲讀背面之注意事項再填寫本頁) 經濟部中央標準局員工消費合作社印製 100 μ Μ引物4 (導入變異用） 1 α 1 ExTaq (寶酒造公司） 0.5/il 導入各種變異時，祗改變引物種類，其他反應組成乃採用相同者。各反應中所使用引物示於表1 〇中，其序列示於序列表中序列號碼2 0 , 2 3 , 2 7， 3 0〜4 0。P C R 1反應液和 P C R 2反應液分別以不同微量離心管裝好，混合後按下列條件進行PCR。971下處理3分鐘後，在95°C下1分鐘，55 °C下1分鐘，7 2 υ下3分鐘，以上述3階段反應重複2 5次後，在7 0 °C下保溫5分鐘。取反應液之一部分進行瓊脂糖本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 51 3 8 0 7 6 538049 A7 B7 五、發明説明（52 ) 電泳分離，確認目的長度的DNA片段達成合成目的。第一階段之P C R反應結束後，從反應液中利用A m i c ο n m i c r 〇 c ο η (A m i c ο n公司製品）去除引物，藉無菌蒸餾水調整最終溶液量為5 0 μ 1，使用所得D Ν Α片段再進行第二階段的P C R反應（ PCR3)〇 PC R 3；?應液 1 0 X E X T a q緩衝液（寶酒造公司） 10 α 1 2.5mMdNTP 溶液 8 //13 8 0 7 6 538049 A7 B7 V. Description of the invention (5!) P C R 1 and P C R 2). PCR 1 g reaction solution 10 0 XEXT aq buffer (Takara Shuzo Co., Ltd.) 2.5mM dNTP solution The plasmid vector (8 ng / m 1) described in Example 1 sterile distilled water 2 0 / i Μ primer 1 100 u Μ primer 2 (introduced For mutation) Ex Ta < i (Takara Shuzo Co., Ltd.) PCR2g Teng solution 10X Ex Taq buffer (Yu Shuzo Co., Ltd.) 2.5 m M d NTP solution The plasmid vector (8ng / ml) described in Example 11 sterile distilled water 20 w Μ Bow I Object 3 10 ^ 1 u 73. U 10 uu 73.5α 1 u (Please read the precautions on the back before filling out this page) 100 μM Primer 4 printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (for introduction of mutation) 1 α 1 ExTaq (Takara Shuzo Co., Ltd.) 0.5 / il When various mutations are introduced, the primer types are changed. The other reaction components are the same. The primers used in each reaction are shown in Table 10, and their sequences are shown in the sequence listing with the sequence numbers 20, 23, 27, 30 to 40. P C R 1 reaction solution and P C R 2 reaction solution were packed in different microcentrifuge tubes, and PCR was performed under the following conditions after mixing. After 3 minutes of treatment at 971, 1 minute at 95 ° C, 1 minute at 55 ° C, and 3 minutes at 7 2 υ, the above-mentioned three-stage reaction was repeated 25 times, and then kept at 70 ° C for 5 minutes. Take a part of the reaction solution for agarose. The paper size applies the Chinese National Standard (CNS) A4 specification (210X 297 mm) 51 3 8 0 7 6 538049 A7 B7 V. Description of the invention (52) Electrophoresis separation to confirm the DNA of the target length Fragments serve the purpose of synthesis. After the completion of the first-stage PCR reaction, the primers were removed from the reaction solution using A mic ο nmicr 〇c ο η (manufactured by A mic ο n), and the final solution amount was adjusted to 50 μ 1 by sterile distilled water. The resulting D Ν was used The Α fragment was then subjected to the second-stage PCR reaction (PCR3). 0 PC R 3;? Application solution 1 0 XEXT aq buffer (Takara Shuzo Co.) 10 α 1 2.5mM dNTP solution 8 // 1

由PCR1所得DNA片段 5 u I 由PCR2所得DNA片段 5 u 1 無舖蒸餾水 6 1 . 5 w 1 2 0 /i Μ 引物 1 5 u 1DNA fragment obtained from PCR1 5 u I DNA fragment obtained from PCR2 5 u 1 distilled water without plating 6 1. 5 w 1 2 0 / i Μ primer 1 5 u 1

20wM引物 3 5 u I20wM primer 3 5 u I

ExTaq (寶酒造公司） 0,5/ilExTaq (Treasure brewing company) 0,5 / il

Μ_UL (請先閱讀背面之注意事項再填寫本頁)Μ_UL (Please read the notes on the back before filling this page)

、1T —φ, 經濟部中央標準局員工消費合作社印製, 1T —φ, printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs

變異體名稱引物1 引物2 引物3 引物4 0C IF-C19S IF10 C19SR IF3 C19SF 0C IF-C20S IF 1 0 C20SR IF3 C20SF 0C IF-C21S IF10 C21SR IF3 C21SF 0C IF-C22S IF10 C22SR IF14 C22SF 0C IF-C23S IF6 C23SR IF14 C23SF 3 8 0 7 6 本紙張尺度適用中國國家標準（CNS ) Α4規格（210Χ297公釐） 52 538049 A7 B7 經濟部中央標準局員工消費合作社印製五、發明説明) 上述溶液放入微量離心管中，混合後按照P C R 1 , PCR2相同條件下進行PCR反應。取反應液之一部分進行瓊脂糖電泳（K或1 , 5 % )分離，確認獲得目的長度之D N A片段已合成。由P C R法所得D N A以乙醇沈澱處理，在真空下乾燥，並溶解在40 /i 1的無菌蒸餾水中。將含有C19S變異DNA 片段的溶液稱為溶液A,含有C20S變異DNA片段的溶液稱為溶液B,含有C21S變異DNAH段的溶液稱為C,含有C22S變異DNA片段的溶液稱為D,含有C23S變異DNA片段的溶液則稱為溶液E。溶液A 2 0 /i 1中的D N A Η段以限制_ N d e I和S p h I (寶酒造公司製品）切割之。由調製用電泳法將約400 bp的DNA片段分離、精製，然後溶解在20/il蒸餾水中做為DNA溶液（3 )。其次，將2iUg的PSK + -0CIF用限制_NdeI和SphI(寶酒造公司製品）切割，由調製用電泳法將約4 . 2 k b的D N A片段分離•精製，然後溶解在20 ^ ]的無蒸餾水中做為DNA溶液 (4 )。將2 u 1的D N A溶液（3 )和3 α 1的D N A溶液（4 )混合，再添加D N A連接用組劑V e r . 2 I液5 /i ]而進行連接反應。使用反應後的連接溶液5 ^ 1 ,進行大腸_ D Η 5 ex的轉化。由D N A 構造分析，從所得耐安比西林細胞中篩選得具有目的質粒 DN A的細胞株。上述DNA構造分析乃由限制酶切割後所得片段長度之測定和決定其塩基序列而達成之。所得具有目的質粒 DNA稱其為 pSK-0CIP-C19S。溶液B 2 0 // 1中的C 2 0 S變異D N A片段，用限制_ H d e I和 S p h I (寶酒造公司製品）切割之。以調製用電泳法將約 (請先閱讀背面之注意事項再填寫本頁) 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 53 3 8 0 7 6 538049 A7 _________ B7 五、發明説明（5 4 ) 400bp的DNA片段分離•精製，然後溶解在20it/l的無菌蒸餾水中做為DNA溶液（5)。將2#1的DNA溶液（5)和3/il的 DNA溶液（4)混合，再添加5//1的DNA連接用組劑Ver.2I液進行連接反應。使用5/il的反應後連接溶液，進行大腸菌 DH5<x之轉化。所得耐安比西林轉化細胞中藉DNA構造分析篩選得具有目的質粒DN A的細胞株。上述DN A構造乃用限制酶切割後所得Η段長度和決定其塩基序列而解析之。所得具有目的質粒DHA稱之為PSK_0CIF-C20S。經濟部中央標準局員工消費合作社印製溶液C 20w 1中的DNA片段用限制酶Ndel和SphI(寶酒造公司製品）切割之。由調製用電泳法將約400bp的DNA片段分離♦精製，溶解在20α 1的蒸餾水中做為DHA溶液（6) 。將2/il的DNA溶液（6)和3/il的DNA溶液（4)混合，再添加 1的DNA連接用組劑Ver.2I液而進行連接反應。使用 5/il的反應後連接溶液，進行大腸菌DH5a之轉化。所得耐安比西林轉化細胞中，由DNA構造分析篩選得具有目的質粒DNA之細胞株。上述DNA構造分析乃由限制酶所切割得 Η段長度測定和決定其塩基序列而解析之。所得目的質粒 DNΑ命名為 pSK-OC IP-C21S。溶液D 20al中的DNAH段用限制酶Ndel和BstPI(寶酒造公司製品）切割之。由調製用電泳法將約600bp的DNA片段分離•精製，然後溶解在20it/ 1的蒸餾水中做為DNA溶液 (7)。其次，將 2wg 的 PSK + -0CIF 用限制 SlHdel 和 BstPI(寶酒造公司製品）切割。由調製用電泳法將約4.Okb的DNA片段分離•精製，溶解在20/il的蒸離水中做為DNA溶液（8) 38076 (請先閱讀背面之注意事項再填寫本頁) 本紙張尺度適用中國國家標準（CNS ) A4規格（21〇X297公釐） 5 4 538049 A7 --B7 五、發明説明（5 5 ) —^_———一 ° 之DNA溶液（7)和3W1的DNA溶液（8)混合後，再添 1的DNA連接用組劑Ver.2I液而進行連接反應。使用 5/il之連接反應後之連接溶液，進行大腸菌DH5a之轉化。所得耐安比西林轉化細胞中，由DNA構造分析而篩選得胃？有目的質粒DHA之細胞株。上述DNA構造之分析乃由限制酶切割所得片段長度之测定以及決定其塩基序列而解析之 Ο 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) 溶液E 20//1中的DNAH段用限制_BstI和EcoRV(寶酒造公司製品）切割之。由調製用電泳法將約12〇bp之DNA片段分離♦精製，然後溶解在20m 1的無_蒸餾水中做為DNA 溶液（9)。其次，將2iug的PSK + -0CIF用限制酶BstEII和 GcoRv (寶酒造公司製品）切割，由調製用電泳法將約4.5kb 的DNAM段分離♦精製，溶解在20// 1的蒸餾水中做為DNA 溶液（10)。將2/z 1的DNA溶液（9)和3/u 1的DNA溶液（10)混合，再添加5/il的DNA連接用組劑νπ·2Ι液進行連接反應。使用5/il的反應後連接溶液，進行大腸薗DH5ot之轉化。所得耐安比西林轉化細胞中，由DN A構造分析篩選得具有目的質粒DNA的細胞株。上述DNA構造分析乃由限制酶切割所得Η段長度測定和決定其塩基序列而解析之。所得目的質粒DNA命名為PSK-0CIP-C23S。 (2)礬里騁裘現媒介物夕嫌链將所得目的之質粒〇^(0$1(-〇(：1?-(：195,0$1(-〇(：1?-C20S, PSK-0CIF-C21S, pSK-〇CIF-C22S, PSK-0CIF~23S) 用限制II BamH I和Xho I (寶酒造公司製品）切割，把含有本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 55 3 807 6 538049 A7 經濟部中央標準局員工消費合作社印製 B7 _________五、發明説明（56 ) OCIPcDNA的全長約1.6kb的DNA片段（包括目的之變異在内）分離•精製，然後溶解在無菌蒸餾水20// 1中。並分別命名為C19S DNA溶液，C20S DNA溶液，C21S DHA溶液， C22S DNA溶液，C23S DNA溶液。其次，將5//g的表現媒介物pCEP4(Invitogene公司製品）用限制_ BaniHI和Zhol (寶酒造公司）切割，分離♦精製得約的DNA,並溶解在 40/i 1的無蒸餾水中做為PCEP4 DHA溶液。將1/i 1的PCEP4 DNA溶液和各為6/il的C19S DNA溶液，C20S DNA溶液， C21S DNA溶液，C22S DNA溶液，C23 SDNA溶液分別混合，在各混合液中添加7// 1的DNA連接用組劑Ver2I液而進行連接反應。反應終了後，使用7m 1之反應液進行大腸菌 DH5a Competent細胞液100/i 1之轉化。從所得耐安比西林轉化細胞選得在PCEP4的Zhol, BaiaHI部分插人有約 1.6kb的各個DNA片段的目的構造質粒DNA共5種細胞株，分別命名為 PCEP4-0CIF-C19S, PCEP4-0CIF-C20S, PCEP4-0CIF-C21S, PCEF4-0C IF-C22S , pCEP4 - 0C I F-C23S 〇 ii) 功能部份番白皙缺牛戀里體毅作 (Ί )功能部位蒂白皙缺生礬里$灌入序列號碼4所載胺基酸中，製作自第2個Thr至第42 値的Ala止，從第43個的Pro至第84餹的Cys止，從第85個的Glu至第122個的Lys止，第123個的Arg至第164値的Cys 止，從177個的Asp至第251個的Gin止，第253個的lie至第 326個的His止，分別缺失的變異體並按加以命名之。由第 2個之Thr至第42個AU止缺失的變異體命外為0CIF-DCR1, (請先閱讀背面之注意事項再填寫本頁) 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 56 3 8 0 7 6 538049 A7 B7 五、發明説明（57 ) 從第43個的Pro至第84個的Cys止缺失的變異體稱為0CIP-DCR2,從第85個的Glu至第122個的Lys止缺失的變異體稱為0CIF-DCR3,從第123個的Arg至第164値的Cys止缺失的變異體稱為0CIF-DCR4，從第177個的Asp至第251個的Glu 止缺失的變異稱為0CIF-DDD1,從第253個的lie至第326個的His止缺失的變異體稱為0CIF-DDD2。導入功能部位蛋白質缺失變異，也按照實施例22-ii)項所記述的二階段PCR 法進行。各變異導入反應時所使用引物示於表11中，其序列分別示於序列表中之序列號碼19，25, 40〜53以及54。裹 11Variant name Primer 1 Primer 2 Primer 3 Primer 4 0C IF-C19S IF10 C19SR IF3 C19SF 0C IF-C20S IF 1 0 C20SR IF3 C20SF 0C IF-C21S IF10 C21SR IF3 C21SF 0C IF-C22S IF10 C22SR IF14 C23SR IF14 C23SF 3 8 0 7 6 This paper size is applicable to Chinese National Standard (CNS) A4 size (210 × 297 mm) 52 538049 A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention) Put the above solution into a microcentrifuge In the tube, perform PCR reaction under the same conditions as PCR 1 and PCR 2 after mixing. Take a part of the reaction solution and separate it by agarose electrophoresis (K or 1, 5%), and confirm that the DNA fragment of the target length has been synthesized. D N A obtained by the PCR method was treated with ethanol precipitation, dried under vacuum, and dissolved in sterile distilled water at 40 / i 1. The solution containing the C19S mutant DNA fragment is called solution A, the solution containing the C20S mutant DNA fragment is called solution B, the solution containing the C21S mutant DNA H segment is called C, and the solution containing the C22S mutant DNA fragment is called D, which contains the C23S mutation The solution of the DNA fragment is called solution E. The D N A segment in solution A 2 0 / i 1 was cut to limit _ N d e I and Sp h I (products of Takara Shuzo Co., Ltd.). A DNA fragment of about 400 bp was separated and purified by electrophoresis with modulation, and then dissolved in 20 / il distilled water as a DNA solution (3). Next, 2iUg of PSK + -0CIF was cut with restriction _NdeI and SphI (produced by Takara Shuzo Co., Ltd.), and a DNA fragment of about 4.2 kb was separated and purified by electrophoresis, and then dissolved in 20 ^] of non-distilled water. As a DNA solution (4). 2 u 1 of the D N A solution (3) and 3 α 1 of the D N A solution (4) were mixed, and then the D N A linking agent V er. 2 I solution 5 / i] was added to perform a ligation reaction. Using the ligation solution 5 ^ 1 after the reaction, the large intestine _ D Η 5 ex was transformed. Based on the D N A structure analysis, a cell line having the target plasmid DN A was selected from the obtained ampicillin-resistant cells. The above DNA structure analysis was achieved by measuring the length of the fragment obtained after restriction enzyme cleavage and determining its fluorenyl sequence. The obtained plasmid DNA of interest is called pSK-0CIP-C19S. The C 2 0 S mutation D N A fragment in the solution B 2 0 // 1 was cut with the restriction _ H de e I and S p h I (products of Takara Shuzo Co., Ltd.). Use the electrophoresis method for modulation (please read the precautions on the back before filling in this page) This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) 53 3 8 0 7 6 538049 A7 _________ B7 V. Invention Explanation (5 4) A 400bp DNA fragment was separated and purified, and then dissolved in 20it / l of sterile distilled water as a DNA solution (5). The DNA solution (5) of 2 # 1 and the DNA solution (4) of 3 / il were mixed, and then 5 // 1 of the DNA ligation reagent Ver. 2I solution was added to perform the ligation reaction. The solution was ligated after a 5 / il reaction to transform E. coli DH5 < x. The obtained ampicillin transformed cells were screened by DNA structure analysis to obtain a cell line having the target plasmid DNA. The DNA structure described above was analyzed using restriction enzyme cleavage to determine the length of the amidine segment and determine its amylase sequence. The resulting plasmid DHA with the objective was called PSK_0CIF-C20S. The DNA fragment in solution C 20w 1 printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs was cut with restriction enzymes Ndel and SphI (products of Takara Shuzo Co., Ltd.). A DNA fragment of about 400 bp was separated and purified by electrophoresis, and dissolved in 20α 1 of distilled water as a DHA solution (6). A 2 / il DNA solution (6) and a 3 / il DNA solution (4) were mixed, and 1 DNA ligation reagent Ver. 2I solution was added to perform a ligation reaction. The reaction solution was used after 5 / il reaction to transform E. coli DH5a. Among the obtained transformed cells resistant to ampicillin, a cell line having the desired plasmid DNA was selected by DNA structure analysis. The analysis of the above-mentioned DNA structure is based on the determination of the length of the amylase fragment cut by the restriction enzyme and the determination of its amyloid sequence. The resulting plasmid DNA was named pSK-OC IP-C21S. The DNAH segment in the solution D 20al was cut with restriction enzymes Ndel and BstPI (products of Takara Shuzo Co., Ltd.). DNA fragments of about 600bp were separated and purified by electrophoresis with modulation, and then dissolved in 20it / 1 distilled water as a DNA solution (7). Secondly, cut 2wg of PSK + -0CIF with the restriction SlHdel and BstPI (products of Baoshu Brewery Co., Ltd.). The DNA fragment of about 4.0kb was separated and purified by electrophoresis, and dissolved in 20 / il of distilled water as the DNA solution (8) 38076 (Please read the precautions on the back before filling out this page) This paper size Applicable to China National Standard (CNS) A4 specification (21 × 297 mm) 5 4 538049 A7 --B7 V. Description of the invention (5 5) — ^ _——— One degree of DNA solution (7) and 3W1 DNA solution (8) After mixing, a further DNA ligation reagent Ver. 2I solution was added to perform ligation reaction. The ligation solution after the ligation reaction at 5 / il was used to transform E. coli DH5a. Among the obtained ampicillin-transformed cells, the stomach was selected by DNA structure analysis. A cell line of the target plasmid DHA. The analysis of the above DNA structure is based on the determination of the length of the fragment obtained by restriction enzyme cleavage and the determination of its base sequence. It is printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling this page) The DNAH segment in // 1 is cut with the restriction _BstI and EcoRV (product of Baoshu Brewery Co., Ltd.). A DNA fragment of about 120 bp was separated and purified by electrophoresis with modulation, and then dissolved in 20 ml of distilled water as a DNA solution (9). Next, 2iug of PSK + -0CIF was cut with restriction enzymes BstEII and GcoRv (manufactured by Takara Shuzo Co., Ltd.), and the 4.5M DNAM segment was separated by purification by electrophoresis. ♦ Refined, dissolved in 20 // 1 distilled water as DNA. Solution (10). The 2 / z 1 DNA solution (9) and the 3 / u 1 DNA solution (10) were mixed, and then a 5 / il DNA ligation reagent νπ · 2I solution was added to perform the ligation reaction. Use a 5 / il reaction to connect the solution to transform the large intestine DH5ot. Among the obtained ampicillin-resistant transformed cells, a cell line having the plasmid DNA of interest was selected by DNA structure analysis. The DNA structure analysis described above was analyzed by determining the length of the amylase segment obtained by restriction digestion and determining the amyloid sequence. The resulting plasmid DNA was named PSK-0CIP-C23S. (2) The target plasmid, which is obtained from the present medium, will be obtained. (0 $ 1 (-〇 (: 1?-(: 195,0 $ 1 (-〇 (: 1? -C20S, PSK-0CIF) -C21S, pSK-〇CIF-C22S, PSK-0CIF ~ 23S) Cut with restriction II BamH I and Xho I (products of Baoshu Brewery Co., Ltd.). The paper containing this paper applies the Chinese National Standard (CNS) A4 specification (210X 297 mm) ) 55 3 807 6 538049 A7 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs B7 _________ V. Description of the Invention (56) OCIPcDNA DNA fragment of about 1.6kb in length (including the variation of the purpose) Isolation, purification, and dissolution In sterile distilled water 20 // 1. And named as C19S DNA solution, C20S DNA solution, C21S DHA solution, C22S DNA solution, C23S DNA solution. Secondly, 5 // g performance medium pCEP4 (manufactured by Invitogene) Cut with restriction _ BaniHI and Zhol (Takara Shuzo Co., Ltd.) to cut and isolate the purified DNA and dissolve it in 40 / i 1 of non-distilled water as a PCEP4 DHA solution. Use 1 / i 1 of the PCEP4 DNA solution and 6 / il of C19S DNA solution, C20S DNA solution, C21S DNA solution, C22S DNA solution, C23 SDNA solution, respectively, To each mixed solution, 7 // 1 DNA ligation reagent Ver2I solution was added to perform the ligation reaction. After the reaction was completed, a 7 ml 1 reaction solution was used to transform the coliform DH5a Competent cell liquid 100 / i 1. Five transformed cell lines of the target construct plasmid DNA with approximately 1.6 kb of each DNA fragment were inserted into Zhol and BaiaHI of PCEP4 transformed cells. They were named PCEP4-0CIF-C19S, PCEP4-0CIF-C20S, PCEP4- 0CIF-C21S, PCEF4-0C IF-C22S, pCEP4-0C I F-C23S 〇ii) Functional part is white and lack of cattle love body body work (Ί) Functional part is white and lack of alum $ Infusion sequence number 4 Among the contained amino acids, Ala from the 2nd Thr to the 42nd ，, Pro from the 43rd to the Cys from the 84th ，, and Glu from the 85th to the 122nd Lys, The 123rd Arg to the 164th Cys stop, the 177th Asp to the 251th Gin stop, the 253th lie to the 326th His stop, were missing variants and named accordingly. The mutants missing from Thr to 42nd AU were 0CIF-DCR1, (Please read the precautions on the back before filling this page) This paper size applies Chinese National Standard (CNS) A4 specification (210X 297 (Mm) 56 3 8 0 7 6 538049 A7 B7 V. Description of the invention (57) The variant from the 43rd Pro to the 84th Cys stop deletion is called 0CIP-DCR2, and from the 85th Glu to the 8th The 122 variants of Lys stop deletion are called 0CIF-DCR3, and the variants of Cys stop deletion from 123rd Arg to 164 値 are called 0CIF-DCR4, from Asp of 177th to Glu of 251th The non-deletion variant is called 0CIF-DDD1, and the His-deletion variant from 253th to 326th is called 0CIF-DDD2. The introduction of a functional site protein deletion mutation was also performed according to the two-stage PCR method described in Example 22-ii). The primers used in the introduction of each mutation are shown in Table 11, and the sequences are shown in the sequence number 19, 25, 40 to 53, and 54 respectively. Wrap 11

變異體名稱引物1 引物2 引物3 引物4 0C IF-DCR1 ZholF DCR1R IF2 DCR1F 0C IF-DCR2 ZholF DCR2R IF2 DCR2F 0C IF-DCR3 ZholF DCR3R IF2 DCR3F 0C IF-DCR4 ZholF DCR4R IF16 DCR4F 0C IF-DDD1 IF8 DDD1R IF14 DDD1F 0C IF-DDD2 IF8 DDD2R IF14 DDD2F 經濟部中央標準局員工消費合作社印製 (請先閲讀背面之注意事項再填寫本頁)Variant name Primer 1 Primer 2 Primer 3 Primer 4 0C IF-DCR1 ZholF DCR1R IF2 DCR1F 0C IF-DCR2 ZholF DCR2R IF2 DCR2F 0C IF-DCR3 ZholF DCR3R IF2 DCR3F 0C IF-DCRDR4F1 DC1 DDD1F 0C IF-DDD2 IF8 DDD2R IF14 DDD2F Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (Please read the precautions on the back before filling this page)

由PCR法所得DNA,用乙醇使之沈澱，在真空中乾燥· 然後溶解於40/il之無菌蒸餾水。含DCR1變異DNA片段的溶液稱為溶液F,含有DCR2變異DNA片段的溶液稱為溶液G, 含有DCR3變異DNAH段的溶液稱為溶液Η ,含DCR4變異DNA 本紙張尺度適用中國國家標準（CNS ) Α4規格（21〇Χ 297公釐） 5 7 3 8 07 6 538049 A7 B7 經濟部中央標準局員工消費合作社印製五、發明説明（58 ) 片段的溶液稱為溶液I,含有DDD1變異DNA片段的溶液稱為溶液J,含有DDD2變異DNA片段的溶液稱為溶液K。將20 μ 1溶液P中之DNA片段以限制酶Ndel和Zhol (寶酒造公司製品）切割之。由調製用電泳法將約500bP的DNA 片段分離•精製，溶解在20以1之無_蒸餾水中做為DNA溶液（11)。其次，將 2/ig 之 PSK + -0CIF甩限制 _NdeI 和 ZhoI( 寶酒造公司製品）切割，由調整用電泳法將約4.0kb之DNA 片段分離•精製，溶解於20" 1之無菌蒸餾水中做為DNA溶液（12)。將2以1之DNA溶液（11)和3/i 1之DNA溶液（12)混合，再加以1之DNA連接用組劑Ver.2I液而進行連接反應。使用反應後之連接溶液5 μ 1進行大腸菌D Η 5 α之轉化。所得耐安比西林轉化細胞中，由DHA構造分析，篩選得導入有目的變異的質粒DNA在OCIFcDNA之細胞株。上述DNA構造分析乃由限制酶切割所得片段長度之測定以及決定其塩基序列而解析之。所得目的之質粒DNA命外為pSK-〇C IF0DCR1 〇 2 0 /i 1溶液G中之D N A片段用限制SI N d e I和Z h ο I (寶酒造公司製品）切割之。由調製用電泳法將約50 0 bp之DNA片段分離♦精製，溶解在20m 1之無菌蒸餾水中稱為DNA溶液 (13)〇將2//1之DNA溶液（13)和3/il之DNA溶液（12)混合，切酶制限用乃析進—之 nd® h 分而 i 造 — 湯 β Ξ大Afi構 2 行DNHA er進由D /液，溶中接胞連細的化後轉 DH應林之反西 1之比 1安 /i 入 5 耐加用得再使所 iu 劑組用接 Ο 〇具應化選反轉篩接之，連 α 析行Η5分 (請先閱讀背面之注意事項再填寫本頁) 述上 ο 株胞細之 A Μη D 粒質的巨有本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 58 3 80 7 6 538049 A7 B7 經濟部中央標準局員工消費合作社印製五、發明説明（5 9 ) 割所得片段長度之测定和決定其塩基序列而解析之。所得目的質粒DNA命名為PSK-0CIF-DCR2。 2〇wl溶液Η中的DNA片段用限制酶Ndel和Zhol(寶酒造公司製品）切割之。由調製用電泳法將約500bp之DNA片段分離♦精製，溶解於20// 1之無菌蒸餾水中稱為DNA溶液 (14)。將2/i 1之DNA溶液（14)和3/i 1之DNA溶液（12)加以混合，再添加5//1之DNA連接用組劑Ver.2I液而進行連接反應。使用5//1之反應後連接溶液進行大腸菌DH5a之轉化。所得耐安比西林轉化細胞中，由DNA之構造分析，篩選得導入目的變異的質粒DNA在OCIFcDNA上的轉化細胞株。上述DN A構造之分析，乃由限制酶切割所得片段長度之測定以及決定其塩基序列而解析之。所得目的之質粒DHA命名為 PSK-0CIF-DCR3。 2〇wl的溶液I中之DHA片段用限制酶Zhol和SphI(寶酒造公司製品）切割之。由調製用電泳法將約900bp之DNA 片段分離•精製，溶解於20^1之無S蒸餾水中稱為DNA溶液（15)。其次，將 2/ig 的 PSK + -0CIF用限制 BSZhoI 和 Sphl( 寶酒造公司製品）切割，由諝製用電泳法將約3.6kb之DNA Μ段分離♦精製，溶解在20/i 1之無菌蒸餾水中做為DNA溶液（16)。把1之DNA溶液（15)和3/i 1之DNA溶液（16)混合 ,再加入1之DNA連接用組劑Ver^2I液而進行連接反應。使用5^1之反應後連接溶液進行大腸菌DH5a之轉化。由所得耐安比西林轉化細胞中，藉DNA構造分析篩選得具有目的質粒DNA之轉化細胞株。上述DNA構造分析乃由限制 (請先閱讀背面之注意事項再填寫士本頁) 本紙張尺度適用中國國家標準（CNS ) A4規格（210 X 297公釐） 538049 A7 B7 五、發明説明（6〇 ) _切割所得Μ之長度测定和決定其塩基序列而解析之。所得目的之質粒DNA命名為i>SK-0CIF-DCR4。將20//1之溶液J中的DNA片段用限制酶BstP]^nNcleI( 寶酒造公司製品）切割之。由調製用電泳法將約4001)1>之 DNA片段分離♦精製，溶解在20^1之無菌蒸餾水中做為 DNA溶液（17)。將2/i 1之DNA溶液（17)和3/i 1之DNiU容液（8) 混合，再加入5m1之DNA連接用組劑Ver2I液而進行連接反應。使用5/il之反應後連溶液進行大腸菌DH5a之轉化。所得耐安比西林轉化細胞中，據DNA構造之分析，舖選得具有目的質粒DHA之轉化細胞株。上述DNA構造之分析，乃由限制酶所切割而得片段之長度測定和決定其塩基序列而解析之。所得之目的質粒DNA命名為pSK-OCIF-DDDI。 (2)戀S艚弃頊載體之構築- 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) 所得之目的質粒1)}^(卩51(-〇(：1卜〇〇1?1，0$1(；-〇(：^_〇(^2 ,PSK-0CIP-DCR3, pSK-0CIF-DCR4, pSK-OCIF-DDDI， PSK-0CIF-DDD2)用限制Bl BamHI和Zhol(寶酒造公司製品）切割，將含OCIFcDHA的全長約1.4〜1.5kb之DHAM段（包括目的之變異）分離♦精製，溶解在20m 1的無菌蒸餾水，而分別命外為DCR1DNA溶液，DCR2DNA溶液，DCR3DNA溶液， DCR4DNA溶液，DDD1DNA溶液，DDD2DHA溶液。將實施例22-ii)項所記載的PCEP4DNA溶液1/i 1和各為6/i 1的上述 DCR1DHA溶液，DCR2DNA溶液，DCR3DNA港液，DCR4DNA溶液 ,DDD1DNA溶液，DDD2DNA溶液個別混合，各混合液中加入 7wl之DHA連接緩衝液而進行連接反應。反應終了後，使本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 6 〇 3 8 0 7 6 538049 A7 B7 五、發明説明（61 ) 用7 // 1之反應液，進行大腸M D Η 5 α之轉化。所得耐安比西林轉化細胞中選擇合計6種在pCEP4BamHI, Zhol部位各插入有1.4〜1.5kb的片段的質粒DNA構造的細胞株。具有上述目的構造的質粒分別命名為PCEP4-0CIF-DCR1, PCEP4-0CIF-DCR2, pCEP4 - 0C I F - DCR3 , pCEP4-0CIF-DCR4, pCEP4~0C IF-DDD1, pCEP4-0CIF-DDD2〇經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) iii)c末端功能部位蒂白皙缺牛礬異體餺作 (1)C未緦功能部位番白皙缺生變累：> 灌入製作序列號碼4中所記載胺基酸中，分別缺失第3 7 9 個的Cys和第380個的Leu,缺失第331個的Ser至第380個的 Leu,缺失第252個的Asp至380値的Leu,缺失第177個的 Asp至第380個的Leu,缺失第123個的Arg至第380個的Leu, 缺失第68個的Cys至第380個的Leu的各種缺失變異體。並分命名上述缺失之變異體，如命名第379個的Cys和第380 値的Leu缺失的變異體為0CIF-CL,自第331個的Ser至第 380個的Leu為止缺失的變異體命名為0CIF-CC,自第252個的Asp至第380個的Leu為止缺失的變異體命名為0CIF-CDD2,自第177個Asp至第380個Leu為止缺失的變異體為 0CIF-CDD1,自第123個的Arg至第380個的Leu為止缺失的變異體為0CIF-CCR4,自第86個的Cys至第380個的Leu為止缺失的變異體命名為0CIP-CCR3。製作變異體0CIF-CL時所導人變異，按照實施例22-ί i )項所記述之二階段P C R方法進行。導入變異反應時所應用的引物示於表1 2中，其塩基序列分別示於序列表中的序本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 6 1 3 80 7 6 538049 A7 B7 五、發明説明（62 ) 列號碼23, 40, 55和56。由PCR法所得DNA以乙醇使之沈麟 ,在真空中乾燥，並溶解在40/il的無S蒸餾水中做為溶液（L )。 20/i 1的溶液（L)中的DNA片段使用限制酶BstPI和 EcoRV (寶酒造公司製品）切割之。由調製用電泳法將約 100bP之DNAH段分離•精製，溶解在20 α 1之無菌蒸纟留水中做為DNA溶液（19)。其次，將2/il之DNA溶液（9)和3以1 之實施例2 2 Μ i )項記載之D N A溶液（1 0 )混合，再加入5以1 的DNA連接用組劑Ver.2I液而進行連接反應。使用5/i 1的反應後的連接溶液，進行大腸®DH5a之轉化。所得耐安比西林之轉化細胞中，據DNA構造之分析篩選得具有目的之質粒DNA的轉化細胞株。上述DNA構造之分析乃由測定限制酶切割所得片段之長度和決定其塩基序列而解析之。所得之目的質粒DNA命名為pSK-OCIF-CL。變異體0CIF-CC, 變異體 0CIF-CDD2,變異體 0CIF-CDD1,變異體 0CIF-CCR4, 變異體0CIF-CCR3,製作用之導入變異中使用一階段的 PCR法。其反應條件示如下：經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) C末端功能部位蛋置缺失變異導λ闲PCR反應液 lOXExTaq緩衝液（寶酒造公司） 10 /ilThe DNA obtained by the PCR method was precipitated with ethanol, dried in a vacuum, and then dissolved in 40 / il of sterile distilled water. The solution containing the DCR1 mutant DNA fragment is called solution F, the solution containing the DCR2 mutant DNA fragment is called solution G, and the solution containing the DCR3 mutant DNAH segment is called solution Η, which contains the DCR4 mutant DNA. The paper standards are applicable to Chinese National Standards (CNS) A4 specification (21 × 297 mm) 5 7 3 8 07 6 538049 A7 B7 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (58) The solution of the fragment is called solution I, and the DDD1 variant DNA fragment contains The solution is called solution J, and the solution containing DDD2 mutant DNA fragment is called solution K. The DNA fragment in 20 μ1 of solution P was cut with restriction enzymes Ndel and Zhol (products of Takara Shuzo Co., Ltd.). About 500bP of DNA fragments were separated and purified by electrophoresis, and dissolved in 20 to 1 non-distilled water as the DNA solution (11). Next, cut 2 / ig PSK + -0CIF _NdeI and ZhoI (products of Takara Shuzo Co., Ltd.), adjust and separate approximately 4.0kb of DNA fragment by electrophoresis, and dissolve it in sterile distilled water of 20 " Is the DNA solution (12). Mix 2 to 1 DNA solution (11) and 3 / i 1 DNA solution (12), and then add 1 DNA ligation reagent Ver. 2I solution to perform the ligation reaction. Transformation of coliform D Η 5 α was performed using 5 μ 1 of the ligation solution after the reaction. The obtained ampicillin-resistant transformed cells were analyzed by DHA structure and screened for a cell strain into which OCIFcDNA was introduced as a plasmid DNA with a targeted mutation. The DNA structure analysis described above was analyzed by measuring the length of the fragment obtained by restriction enzyme cleavage and determining its fluorenyl base sequence. The resulting plasmid DNA was unexpectedly cut from the DNA fragment of pSK-oC IF0DCR1 0 2 0 / i 1 solution G with restriction SI N d e I and Z h ο I (products of Takara Shuzo Co., Ltd.). A DNA fragment of about 50 bp is separated by refining and electrophoresis. ♦ Refined, dissolved in 20 ml of sterile distilled water is called DNA solution (13). 2 // 1 DNA solution (13) and 3 / il DNA. The solution (12) is mixed, and the enzyme digestion is limited to precipitation. The nd® h is divided into two. The soup β is a large Afi structure. The DNHA is mixed into D / liquid, and the solution is transferred to DH. The ratio of Yinglin's anti-west 1 ratio is 1 amp / i into 5. If it is resistant to addition, then the iu agent group must be connected with a reversed sieve, and the α analysis line should be 5 points (please read the first Please fill in this page again.) As described above, the size of A Μη D grain of this plant is large. The paper size is applicable to China National Standard (CNS) A4 specification (210X 297 mm) 58 3 80 7 6 538049 A7 B7 Ministry of Economic Affairs Printed by the Consumer Standards Cooperative of the Central Bureau of Standards. 5. Description of the Invention (5 9) The length of the fragment obtained was determined and the base sequence was determined and analyzed. The obtained target plasmid DNA was named PSK-0CIF-DCR2. The DNA fragment in the 20wl solution was cut with restriction enzymes Ndel and Zhol (manufactured by Takara Shuzo Co., Ltd.). DNA fragments of about 500 bp were separated and purified by electrophoresis with modulation, and dissolved in 20 // 1 of sterile distilled water as a DNA solution (14). The 2 / i 1 DNA solution (14) and the 3 / i 1 DNA solution (12) were mixed, and then 5 // 1 of the DNA ligation reagent Ver. 2I solution was added to perform the ligation reaction. The reaction solution was used for transformation of coliform DH5a using 5 // 1 reaction. Among the obtained ampicillin-resistant transformed cells, the transformed cell strain on the OCIF cDNA, into which the plasmid DNA of the target mutation was introduced, was selected by analyzing the DNA structure. The analysis of the DNA structure described above was resolved by measuring the length of the fragment obtained by restriction enzyme cleavage and determining the fluorenyl base sequence. The resulting plasmid DHA was named PSK-0CIF-DCR3. 20wl of the DHA fragment in Solution I was cut with restriction enzymes Zhol and SphI (products of Takara Shuzo Co., Ltd.). A DNA fragment of approximately 900 bp is separated and purified by electrophoresis, and dissolved in 20 ^ 1 S-free distilled water, which is called a DNA solution (15). Next, 2 / ig of PSK + -0CIF was cut with restricted BSZhoI and Sphl (products of Takara Shuzo Co., Ltd.), and the DNA M segment of about 3.6kb was separated by purification by electrophoresis. ♦ Purified and dissolved in sterile distilled water at 20 / i 1 As the DNA solution (16). The DNA solution (1) of 1 and the DNA solution (3) of 3 / i 1 are mixed, and then the DNA ligation reagent Ver ^ 2I solution of 1 is added to perform the ligation reaction. A 5 ^ 1 reaction was used to transform the coliform DH5a using a ligation solution. From the obtained ampicillin-transformed cells, a transformed cell line having the desired plasmid DNA was selected by DNA structure analysis. The above DNA structure analysis is limited (please read the precautions on the back before filling in this page) The paper size is applicable to the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 538049 A7 B7 V. Description of the invention (6〇 ) _ The length of the M obtained by cleavage is determined and determined by analyzing its fluorenyl sequence. The resulting plasmid DNA was named i > SK-0CIF-DCR4. The DNA fragment in the 20 // 1 solution J was cut with the restriction enzyme BstP] nNcleI (product of Takara Shuzo Co., Ltd.). The DNA fragment of about 4001) 1> was separated and purified by electrophoresis with modulation, and dissolved in 20 ^ 1 of sterile distilled water as a DNA solution (17). The 2 / i 1 DNA solution (17) and the 3 / i 1 DNiU container solution (8) were mixed, and then 5 ml of the DNA ligation reagent Ver2I solution was added to perform the ligation reaction. The 5 / il reaction solution was used to transform E. coli DH5a. Among the obtained transformed cells resistant to ampicillin, according to the analysis of the DNA structure, a transformed cell line having the target plasmid DHA was selected. The analysis of the above-mentioned DNA structure is determined by determining the length of the fragment cut by the restriction enzyme and determining its fluorenyl sequence. The resulting plasmid DNA of interest was named pSK-OCIF-DDDI. (2) The construction of the love carrier-printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs (please read the precautions on the back before filling this page) The resulting plasmid 1)} ^ (卩 51 (-〇 ( : 1 〇〇〇１１，0 $ 1 (;-〇 (: ^ _〇 (^ 2, PSK-0CIP-DCR3, pSK-0CIF-DCR4, pSK-OCIF-DDDI, PSK-0CIF-DDD2) restrictions Bl BamHI and Zhol (products of Takara Shuzo Co., Ltd.) were cut, and the DHAM segment containing OCIFcDHA with a length of about 1.4 to 1.5 kb (including the variation of the purpose) was separated. ♦ Refined, dissolved in 20m 1 of sterile distilled water, and the DCR1 DNA solution and DCR2 DNA were named as exception. Solution, DCR3DNA solution, DCR4DNA solution, DDD1DNA solution, DDD2DHA solution. The PCEP4DNA solution 1 / i 1 described in Example 22-ii) and the aforementioned DCR1DHA solution, DCR2DNA solution, DCR3DNA harbor solution each of 6 / i 1, DCR4DNA solution, DDD1DNA solution, DDD2DNA solution are mixed individually, and 7wl of DHA ligation buffer is added to each mixed solution to perform ligation reaction. After the reaction is completed, the paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) 6 〇3 8 0 7 6 538049 A7 B7 V. Description of the invention (61) Use 7 // 1 of The cell solution was used to transform the large intestine MD Η 5 α. Among the obtained ampicillin-resistant transformed cells, a total of 6 cell lines constructed with plasmid DNA having a fragment of 1.4 to 1.5 kb in each of pCEP4BamHI and Zhol were selected. The plasmids were named PCEP4-0CIF-DCR1, PCEP4-0CIF-DCR2, pCEP4-0C IF-DCR3, pCEP4-0CIF-DCR4, pCEP4 ~ 0C IF-DDD1, pCEP4-0CIF-DDD2 Printed (please read the precautions on the reverse side before filling in this page) iii) The c-terminal functional part is white and lacking bovine alum allogeneic operation (1) The C non-functional part is white and lacking and becomes tired: > Fill in the serial number In the amino acid described in 4, the 379th Cys and the 380th Leu are missing, the 331th Ser to the 380th Leu are missing, and the 252th Asp to the 380 ° Leu are missing, respectively. Various deletion variants were deleted from the 177th Asp to 380th Leu, the 123rd Arg to 380th Leu, and the 68th Cys to 380th Leu. The variants with the above deletions are named separately. For example, the 379th Cys and 380th Leu deletion variants are named 0CIF-CL, and the 1-3th Ser to 380th Leu deletion variants are named as 0CIF-CC, variants deleted from Asp 252 to Leu of 380th are named 0CIF-CDD2, variants deleted from Asp 177 to 380 Leu are 0CIF-CDD1, The variant deleted from Arg to Leu of the 380th was 0CIF-CCR4, and the variant deleted from Cys from the 86th to Leu of the 380th was named 0CIP-CCR3. The mutation induced when the mutant 0CIF-CL is produced is performed according to the two-phase PCR method described in Example 22-Ii). The primers used in the introduction of the mutation reaction are shown in Table 12 and the fluorene-based sequences are shown in the sequence list. The paper size is applicable to the Chinese National Standard (CNS) A4 (210X 297 mm) 6 1 3 80 7 6 538049 A7 B7 V. Description of the invention (62) Column numbers 23, 40, 55 and 56. The DNA obtained by the PCR method was allowed to sink in ethanol with ethanol, dried in a vacuum, and dissolved in 40 / il of S-free distilled water as a solution (L). The DNA fragment in the 20 / i 1 solution (L) was cut using the restriction enzymes BstPI and EcoRV (manufactured by Takara Shuzo Co., Ltd.). The DNAH segment of about 100bP was separated and purified by electrophoresis, and dissolved in 20 α 1 of sterile distilled water as a DNA solution (19). Next, 2 / il of the DNA solution (9) and 3 to 1 of the DNA solution (1 0) described in Example 2 2 M i) were mixed, and then 5 to 1 of the DNA ligation reagent Ver. 2I solution was added. Instead, a ligation reaction is performed. Using the ligation solution after the 5 / i 1 reaction, large intestine® DH5a was transformed. Among the obtained transformed cells of anibecillin, a transformed cell line having the desired plasmid DNA was selected based on the analysis of the DNA structure. The analysis of the above-mentioned DNA structure is determined by determining the length of the fragment obtained by restriction enzyme cleavage and determining its fluorenyl sequence. The resulting plasmid DNA of interest was named pSK-OCIF-CL. Variant 0CIF-CC, variant 0CIF-CDD2, variant 0CIF-CDD1, variant 0CIF-CCR4, variant 0CIF-CCR3, and one-stage PCR method was used to make the mutation. The reaction conditions are as follows: Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs (please read the precautions on the back before filling out this page) C-terminal functional site missing egg mutation mutation lambda idle PCR reaction solution lOXExTaq buffer solution (Takara Shuzo Co., Ltd.) 10 / il

2.5raMdNTP溶液 8 u I 實施例11所記載之質粒載體（Sng/nil) 2 w 1 無鋪蒸餾水 73.5/il 20wM 引物 OCIFZhoF 5 u 12.5raMdNTP solution 8 u I The plasmid vector (Sng / nil) described in Example 11 2 w 1 distilled water without plating 73.5 / il 20wM Primer OCIFZhoF 5 u 1

100 a Μ變異導入用引物 1 u I 本紙張尺度適^中國國家標準（CNS ) Α4規格（210X297公釐） 62 38076 538049 A7 B7 五、發明説明（63 )100 a μM primers for mutation introduction 1 u I This paper is suitable for Chinese National Standard (CNS) A4 size (210X297 mm) 62 38076 538049 A7 B7 V. Description of the invention (63)

Ex Taq (寶酒造公司） 0 . 表 12 變異體名稱引物1 引物2 引物3 引物4 0C IF-CL IF6 CLR IF 1 4 CLF 經濟部中央標準局員工消費合作社印製導入各個變異時，祗改變引物之種類，其他反應組成不變。各反應中所用變異導入用之引物示於表13,其序列示於序列表中序列號碼5 7〜6 1。將P C R反應液放入撤量離心管中混合後，按照下列條件進行P C R。在9 7它下處理3 分鐘後，在95°C下30秒鐘，50°C下30秒鐘，701C下3分鐘的三階段反應重複25次後，在7〇υ下保溫5分鐘。將反應液之一部分提供瓊脂糖電泳分析，而確認已合成目的長度之DNA片段。從反應液中藉Amicon Microcon去除引物，以乙醇處理使DNA沈澱，在真空下乾燥，並溶解在40/il的無 _蒸餾水中。將含有各變異DNA片段的20/il溶液中的DNA 片段用限制酶X h ο I和B a m Η I切割D N A。切割終了後，以乙醇處理使DN A沈澱，在真空中乾燥，溶解在20/i 1的無菌蒸餾水中。上述溶液分別命名為C C D N A溶液，C D D 2 D N A溶液， C D D 1 D N A 溶液，C C R 4 D N A 溶液，C C R 3 D N A 溶液。 (請先閱讀背面之注意事項再填寫本頁)Ex Taq (Baoji Brewery Co., Ltd.) 0. Table 12 Variant name Primer 1 Primer 2 Primer 3 Primer 4 0C IF-CL IF6 CLR IF 1 4 CLF When the variation is printed and introduced by the staff consumer cooperative of the Central Standards Bureau of the Ministry of Economic Affairs, please change the primers. Kind, other reaction composition is unchanged. The primers used for the introduction of mutations used in each reaction are shown in Table 13, and their sequences are shown in the sequence listing with sequence numbers 5 7 to 61. The P C R reaction solution was mixed in a withdrawal centrifuge tube, and then P C R was performed under the following conditions. After treating for 3 minutes at 97, the three-stage reaction was repeated 25 times at 95 ° C for 30 seconds, 50 ° C for 30 seconds, and 701C for 3 minutes, and then incubated at 70 ° for 5 minutes. A part of the reaction solution was subjected to agarose electrophoresis analysis, and it was confirmed that a DNA fragment of a desired length had been synthesized. The primers were removed from the reaction solution by Amicon Microcon, and the DNA was precipitated with ethanol treatment, dried under vacuum, and dissolved in 40 / il distilled water. DNA fragments in a 20 / il solution containing each variant DNA fragment were cut with DNA restriction enzymes X h ο I and B a m Η I. After the cutting was completed, DNA was treated with ethanol to precipitate DNA, dried in vacuum, and dissolved in 20 / i 1 of sterile distilled water. The above solutions are named C C D N A solution, C D D 2 D N A solution, C D D 1 D N A solution, C C R 4 D N A solution, and C C R 3 D N A solution. (Please read the notes on the back before filling this page)

、1T 本紙張尺度適用中國國家標準（CNS ) Α4規格（210X297公釐） 63 3 8 0 7 6 538049 A7 B7 五、發明説明（64 ) m_1_1 變異體名稱導入變異用引物 0C IF-CC CCR 0C IF-CDD2 CDD2R 0C IF-CDD1 CDD1R 0C IF-CCR4 CCR4R 0C IF-CCR3 CCR3R (2)轡S體丟規載體之構築 (請先閲讀背面之注意事項再填寫本頁) 經濟部中央標準局員工消費合作社印製將PSK-OCIF-CL以限制酶BamHI和Zhol (寶酒造公司製品）切割，分離•精製得含〇 C I F c D N A的約1 · 5 k b的D N A片段（包含有目的之變異），溶解在20//1無菌蒸餾水做為CLDNA 溶液。將1 /i 1的實施例22-ί丨）項所記載之PCEP4 DNA溶液和各為6 /i 1的各個C L D Ν Α溶液，C C D Ν Α溶液，C D D 2 D Ν Α溶液， C D D 1 D N A溶液，C C R 4 D N A溶液，C C R 3 D N A溶液分別混合，加入1之DNA連接用組劑Ver.2I液而進行連接反應。反應後使用7 y 1之反應液進行大腸_ D Η 5 α之轉化。所得耐安比西林轉化細胞中，篩選得具有目的之變異的〇 C I F c D Ν Α片段插人在PCEP4之ZhoI-BamHI部位構造的質粒DNA的轉化細胞株共計六種。上述具有目的構造之質粒分別命外為 PCEP4-0C IF-CL , pCEP4-〇CIF-CC, pCEP4-〇CIF-CDD2, PCEP4-0C IF-CDD1 , PCEP4-〇C IF-CCR4, pCEP4-〇CIF-CCR3 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 64 3 807 6 538049 A7 B7 經濟部中央標準局員工消費合作社印製五、發明説明（65 ) 0 i v ) C末端缺生戀逞鵲^餺作 (1)C末端缺安戀累夕_入製作序列號碼4所記載胺基酸中，自第371個的Gin至第380個的Leu為止缺失而附加以Leu-Val的二殘基的變異體（OCIF-CBst),自第298個的Cys至第380個的Leu為止缺失而附加以Ser-Leu-Asp殘基的變異體（OCIF-CSph),自第 167個Asn至第380個的Leu為止缺失的變異體（OCIF-CBsp), 自第62個的Cys至第380個的Leu為止缺失而附加以Leu -Val二殘基的變異體（OCIF-CPst)。各為 2/ig 的 PSK + -0CIF 用限制酶 BstPI, SphI, Pstl( 寶酒造公司製品）以及B s p E I (新英格蘭B i ο 1 a b公司製品）切割，經酚處理，乙醇沈澱處理而精製得DNA,溶解在10^1 的菌蒸餾水中。使用各為2 /i 1之溶液，藉D N A鈍端化組劑（寶酒造公司製品）將各DNA之末端加以鈍端化處理（最終容量為5/il)。上述反應液中添加含有安伯密碼子（Amber codon)的 Zbal連接物（5’-CTAGTCTAGACTAG-3’）l/i g(lw 1) 和6/i 1的DNA連接用組劑Ver.2I液而進行連接反應。使用 6 α 1的反應後連接溶液進行大腸菌D Η 5 ot之轉化。所得耐安比西林轉化細胞中，據D Ν Α構造分析，篩選得具有目的質粒DHA之轉化細胞株。上述DNA構造分析乃測定由限制酶所切割片段之長度和決定其塩基序列而解析之。所得目的之質粒 DNA分別命名為 pSK-OCIF-CBst, pSK-OCIF-CSph, pSK-OCIF-CBsp, pSK-0CIF~CPst〇 (請先閲讀背面之注意事項再填寫本頁) 衣. _» 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 65 3 8 0 7 6 538049 A7 ____ B7 _ _ 五、發明説明（66 ) 12)礬里鵲弄頊載體少耩铤所得質粒 DNA(pSK-〇CIF-CBst, pSK-OCIF-CSph, pSK-OCIF-CBsp, pSK-OCIF-CPst)用限制酶 BamHI 和 ZhoI( 寶酒造公司製品）切割，分離•精製得含有OCIFcDNA全長約1.5kb的DNAH段（包含目的之變異），溶解在20/ul無菌蒸餾水中（分別命名為CBstDNA溶液，CSphDNA溶液， CBspDNA溶液，CPstDNA溶液）。將實施例22-ii)項所記載之PCEP4DNA溶液lw 1和各為1的CBstDNA溶液， C S p h D N A溶液，C B s p D Η A溶液，C P s t D N A溶液分別混合，各混合液中加入各為7/i 1之DNA連接用組劑Ver.21液而進行連接反應。反應終了後，利用7//1的反應液進行大腸菌 D Η 5 cx之轉化。所得耐安比西林轉化細胞株中篩選得具有目的變異的OCIFcDNA片段插人在PCEP4之ZhoI-BamHI部位間構造的質粒DNA的轉化細胞株合計5種。具有目的構造的質拉分別命名為pCEP-OCIF-CBst, pCEP4-0CIF_CSph, pCEP-OC IF-CBsp, pCEP4 - 0C I F - CPst〇 v) 變異體表現載體之調製經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) 增殖具有變異體表現載體的大腸菌（合計21種類），再使用吉阿研分離管（吉阿研公司製品）精製各種變體表現載體。使用乙醇使各表現載體沈澱後，溶解在無菌蒸餾水中提供後記操作用途。 v Η 戀墨鰐c D N A的钜塹砉現和其活袢測宙使用實施例2 2 - v )項中所精製的各種0 C I F變異體表現質粒，按照實施例13之方法表現出0CIF變異體。下面僅記本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 66 3 8 076 538049 A7 B7五、發明説明（67 ) 述有變更處之要點。導入DNA時使用24洞孔穴盤。將 2X105個的293/EBNA細胞，利用含有10%胎牛血清的 I M D Μ培養基播插在穴盤洞孔中。導入D H A時所使用變異體表現載體和脂費他明（L i p 〇 f e c t a m ί η )量分別為1 μ g和4 u ] 。使用0ΡΤΙ-ΜΕΜ培養基（吉勿可BRL公司製品）稀釋，其最終容量調整為0.5ml。變異體表現載體和脂費他明（ Lipofectamin)之混合添加在細胞中，在37°C,二氧化碳保溫箱中培養24小時後，除去混合液，再加入0.5ml的Ex-細胞301之培養基（JSR公司製品），再在371〇下，二氧化磺保溫箱中培養48小時。回收培養基，做為變異體活性測定用試料。所得各變異體的塩基序列分別示於序列表中號碼 8 3〜1 0 3中，由該序列所推定胺基酸序列示於序列表中序列號碼6 2〜8 2中。0 C I F活性測定按照實施例1 3中所示方法。另外，按照實例24所記述之EIA方法定量0CIF之抗原量。表14中示抗原量單位活性和未改變0CIF之比較結果。 (請先閱讀背面之注意事項再填寫本頁) 經濟部中央標準局員工消費合作社印製本纸張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 3 8 0 7 6 538049 A7 B7 五、發明説明（68 ) 表_14 變異體名稱活性經濟部中央標準局員工消費合作社印製未改變0 C I F + 0C IF-C19S + 0C IF-C20S 士 0C IF-C21S 士 0C IF-C22S + 0C IF-C23S + OCF I-0CR1 士 0C IF-DCR2 士 0C IF-DCR3 土 0C IF-DCR4 士 CO IF-DDD1 + 0C IF-DDD2 士 0C IF-CL + 0C IF-CC + 0C IF-CDD2 + 0C IF-CDD1 + 0C IF-CCR4 士 0C IF-CCR3 士 0C IF-CBst + 0 C I F - C S p h + 0C IF-CBsp 士 0C IF-CPst 士 (請先閱讀背面之注意事項再填寫本頁) 訂 4 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 3 8 0 7 6 68 538049 A7 B7 經濟部中央標準局員工消費合作社印製五、發明説明（6 9 ) (上表中，+ +示抗原量單位的活性超過未改變OCIF之活性之50%者，+示上述活性為10%〜50%，土示活性未滿1 〇 %或無法正確測定抗原量）。 v i )两方墨點解析將使用於活性測定之試料1 0 /i 1提供西方墨點解析用途。10/il的試料中加入ΙΟ/il之SDS-PAGE用試料緩衝液[ 0·5Μ Tris-Hcl, 20% 甘油，4%SDS, 20iug/inl溴酚藍（ PH6.8)],在1001C下煮沸3分鐘，在非還原狀下進行10% SDS聚丙烯醯胺電泳分離。電泳分離後，藉半乾浸漬裝置（ Biorad公司製品）將蛋白質浸在PVDF膜（ProBlott® , Perkin-Elmer公司製品）。該膜封阻後，依據實施例24所記述之EIA用西洋山葵過氧_標記抗0CIF抗體一起在37°C 下保溫2小時。洗淨後藉ECL糸統（Amerskam公司）檢驗結合於抗0CIF抗體之蛋白質。0CIF檢驗有約120kD和60kD的譜帶。另一方面，在 0CIF-C23S, OCIF-CL, 0CIF_CC 幾乎祗能檢驗出60kD之譜帶。S外，0CIF-CDD2和0CIF-CDD1上分別撿出約40 - 5 0 k D和30-40k D之譜帶做為主要譜帶。由上述結果知0CIF上，序列表中序列號碼4的胺基酸序列中第 380個的Cys殘基和二（聚）體型之形成有關，單體型也保持有活性，以及第177値的Asp至第3 80個的Leu為止之殘基缺失也能保持有活性等。 [實施例2 3 ] 人類0CIF某因紐DNA^分離 T ) 人類某因甜DHA種源塵夕篩撰 (請先閱讀背面之注意事項再填寫本頁) 、言 β 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 69 3 8 0 7 6 538049 A7 B7 _____ 五、發明説明（7〇 ) 從Stratagene公司購得使用人肺之染色體DNA和λ ΡΙχΙΙ載體製作的基因組種源庫，再利用OCIFcDNA為探針進行篩選。上述篩選方法，基本上依照基因組種源庫隨附指示進行，但是操作噬菌體，大腸菌，D N A等一般方法乃依照 Malecular Cloning:A Laboratory Manual— 書所記載方法實施。經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) 檢査所購入基因組DNA種源庫之滴定度後，以 !xl〇6pfu的噬菌體感染大腸薗ZLI-Blue MRA，並在20張板上（9x 13c«i)以每張板上9ml的頂部瓊脂糖一起播種之。然後在371C下保溫一夜後，將Hybond-N尼龍膜（Aroersham 公司製品）放置在瓊脂糖板上，將噬菌體加以轉錄。轉錄有噬菌體之尼龍膜，放置在用1·5Μ氯化鈉/ 0.5M氫氧化鈉溶液弄濕的濾紙上一分鐘，然後分別用1Μ的Tris-Hcl( ί>Η7,5)和 1.5M氯化鈉 / 〇·5Μ Tris-Hcl(pH7.5)分別處理一分鐘而中和後，最後移至用2XSSC弄濕的濾紙上。然後在該尼龍膜上利用StratLinker(Stratagene公司製品）照射以1200微焦耳（fflicrojoule)的紫外光（UV)而將噬菌體DNA 固定在膜上。其次，將該膜浸漬在快速雜化緩衝液（ Amersham公司製品）中進行預雜化處理。一小時之預雜化處理後，加人標記有32P的OCIFcDNA,在65Ό下進行雜化處理一夜。該c D N A探針乃將具有實施例1 1所得1 · 6 k b的 OCIFcDHA的質粒pBKOCIF,用限制酶BamHI和Zhol切割’利用瓊脂糖凝_電泳法將0CIPcDNA分離後，將此0CIFcDNM^ 用MegprimeDNA標記条統（Aroersham公司製品）標ώ 32P而製本紙張尺度適用中國國家標準（CNS ) Α4規格（210x297公釐） 7 0 3 8 0 7 6 538049 A7 B7 五、發明説明（7 1 ) 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) 作之。標記依據隨附檫記条統之指示進行。雜化作用時每 lml的雜化作用緩衝液中大約使用5xl05cpro的探針。雜化作用後，在室溫下用2XSSS將尼龍膜洗淨5分鐘。然後在 65°C下用0,5XSSC/0.1%SDS四次，分別洗淨20分鐘。洗淨第4次後，將尼龍膜乾燥，利用富士軟片公司製X光用底片，S U p e r - H R - Η和超感性影幕，在~ 8 0 °C下進行放射自顯術（Autoradiography)處理。在放射自顯譜圖上檢驗有 6個訊息。因此，分別在相對應於該訊息的瓊脂糖板上位置切取上面的瓊脂糖，分別浸漬在添加有1%氯仿的0.5ml SM緩衝液中並放置一夜，再萃取噬菌體。將各個噬菌體萃取液分別用SM緩衝液稀釋為1 0 0 0倍，再取其中的1 /i 1和 20 w 1 ,再感染上述大腸菌，和上述頂部瓊脂糖一起按照上述方法播種在瓊脂糖板上。噬_體轉錄在尼龍膜後，依據上述方法進行預雜化作用，雜化作用，洗淨，乾燥，放射自顯照射等。上述純化噬菌體之操作，就先前在放射自顯譜圖上所檢出的6個訊息部分全部進行，在瓊脂糖板上所有的噬猶體斑點和cDNA探針雜化為止重複操作。切取所純化的噬_體斑點，浸漬在含有1%氯仿的SM緩衝液0.5ml 中，保存在4 °C。據此所得6種純化噬菌體，分別命名為入 0IF3, A0IF8, A0IF9, AOIFll, A0IF12, A0IF17、 1T This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) 63 3 8 0 7 6 538049 A7 B7 V. Description of invention (64) m_1_1 Variation name introduction primer for mutation 0C IF-CC CCR 0C IF -CDD2 CDD2R 0C IF-CDD1 CDD1R 0C IF-CCR4 CCR4R 0C IF-CCR3 CCR3R (2) Construction of S-body Loss Regulation Carrier (Please read the precautions on the back before filling out this page) Staff Consumer Cooperatives, Central Bureau of Standards, Ministry of Economic Affairs Printed and cut PSK-OCIF-CL with restriction enzymes BamHI and Zhol (produced by Takara Shuzo Co., Ltd.), separated and purified to obtain a DNA fragment of about 1.5 kb (including targeted mutations) containing 0CIF c DNA, dissolved in 20 // 1 sterile distilled water was used as the CLDNA solution. The PCEP4 DNA solution described in Example 22-I) of 1 / i 1 and each CLD Ν Α solution, CCD Ν Α solution, CDD 2 D Ν Α solution, and CDD 1 DNA solution described in 6 / i 1 The CCR 4 DNA solution and the CCR 3 DNA solution were mixed separately, and the DNA ligation reagent Ver. 2I solution of 1 was added to perform the ligation reaction. After the reaction, a 7 y 1 reaction solution was used to convert large intestine _ D Η 5 α. Of the obtained anibecillin-transformed cells, a total of six types of transformed cell strains having plasmids of the plasmid DNA constructed at the ZhoI-BamHI site of PCEP4 were screened with the desired mutant OC I F c D N A fragments. The above-mentioned plasmids with the target structures were named PCEP4-0C IF-CL, pCEP4-〇CIF-CC, pCEP4-〇CIF-CDD2, PCEP4-0C IF-CDD1, PCEP4-〇C IF-CCR4, pCEP4-〇CIF- CCR3 This paper size applies Chinese National Standard (CNS) A4 specification (210X 297 mm) 64 3 807 6 538049 A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of invention (65) 0 iv) C-terminal missing Love 逞鹊 ^ 馎 work (1) C-terminal deficient love __ In the amino acid described in the production sequence number 4, from the 371th Gin to the 380th Leu is missing, and the Leu-Val Two-residue variant (OCIF-CBst), deleted from Cys 298 to Leu of 380 and appended with Ser-Leu-Asp residue (OCIF-CSph), from 167 Asn A variant deleted up to the 380th Leu (OCIF-CBsp), a variant deleted from the 62nd Cys to the 380th Leu and added with a Leu-Val two residue (OCIF-CPst). Each 2 / ig PSK + -0CIF was purified with restriction enzymes BstPI, SphI, Pstl (products of Takara Shuzo Co., Ltd.) and B sp EI (products of New England B i ο 1 ab Co.), purified by phenol treatment and ethanol precipitation treatment. DNA was dissolved in 10 ^ 1 of bacteria distilled water. Using a solution of 2 / i 1 each, the ends of each DNA were blunt-end treated with a D N A blunt-end group reagent (product of Takara Shuzo Co., Ltd.) (final capacity was 5 / il). To the above reaction solution was added a Zbal linker (5'-CTAGTCTAGACTAG-3 ') l / ig (lw 1) and 6 / i 1 DNA ligation reagent Ver. 2I solution containing Amber codon. A ligation reaction is performed. The reaction solution of 6 α 1 was used to transform E. coli D Η 5 ot. Among the obtained ampicillin-resistant transformed cells, a transformed cell line having the target plasmid DHA was screened according to the DNA structure analysis. The DNA structure analysis described above is determined by determining the length of the fragment cut by the restriction enzyme and determining its fluorenyl sequence. The resulting plasmid DNA was named pSK-OCIF-CBst, pSK-OCIF-CSph, pSK-OCIF-CBsp, pSK-0CIF ~ CPst〇 (Please read the precautions on the back before filling this page). The paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) 65 3 8 0 7 6 538049 A7 ____ B7 _ _ V. Description of the invention (66) 12) The plasmid DNA obtained by making the carrier less pSK-〇CIF-CBst, pSK-OCIF-CSph, pSK-OCIF-CBsp, pSK-OCIF-CPst) is cut with restriction enzymes BamHI and ZhoI (products of Takara Shuzo Co., Ltd.), and is isolated and purified to obtain DNAH containing OCIFcDNA with a total length of about 1.5 kb. Segment (including the variation of the purpose), dissolved in 20 / ul of sterile distilled water (named CBstDNA solution, CSphDNA solution, CBspDNA solution, CPstDNA solution). The PCEP4DNA solution lw 1 described in Example 22-ii) and the CBstDNA solution, CS ph DNA solution, CB sp D Η A solution, and CP st DNA solution described in each 1 were mixed separately, and each mixed solution was added to each 7 / i 1 DNA ligation reagent Ver. 21 was used for ligation reaction. After the reaction, the E. coli D Η 5 cx was transformed with the 7 // 1 reaction solution. Among the obtained ampicillin-resistant transformed cell lines, a total of five transformed cell lines were selected in which the OCIF cDNA fragment having the desired mutation was inserted into plasmid DNA constructed between the ZhoI-BamHI sites of PCEP4. The mass pulls with the purpose structure are named pCEP-OCIF-CBst, pCEP4-0CIF_CSph, pCEP-OC IF-CBsp, pCEP4-0C IF-CPst〇v) Modulation of the performance vectors of the variants. System (please read the precautions on the reverse side before filling out this page) Proliferate coliforms with a variety of expression vectors (21 types in total), and then use Gyan research isolation tubes (products of Gyan Research) to refine various expression vectors. After each expression vector was precipitated with ethanol, it was dissolved in sterile distilled water for post-operation use. v 墨 The occurrence and liveness of c DNA of the crocodile crocodilus c. The various 0 CIF variant expression plasmids purified in Example 2 2-v) were used to express the 0 CIF variant according to the method of Example 13. . Only the dimensions of this paper are applicable to the Chinese National Standard (CNS) A4 (210X297 mm) 66 3 8 076 538049 A7 B7. The main points of the changes in the description of the invention (67) are described below. Use a 24-well plate for DNA introduction. 2 × 105 293 / EBNA cells were seeded into a hole in a tray using an IM DM medium containing 10% fetal bovine serum. The amount of the variant expression vector and lipophetamine (L i p o f e c t a m ί η) used in the introduction of D H A were 1 μg and 4 u] respectively. It was diluted with OPTI-MEM medium (manufactured by Jebel BRL), and its final volume was adjusted to 0.5 ml. The mutant expression vector and Lipofectamin were added to the cells. After incubation in a carbon dioxide incubator at 37 ° C for 24 hours, the mixture was removed, and 0.5 ml of Ex-cell 301 medium (JSR) was added. Company products), and then incubated at 37 ° C for 48 hours in a sulfur dioxide incubator. The culture medium was recovered and used as a sample for measuring the activity of the variant. The obtained fluorenyl sequences of the respective variants are shown in the sequence number 8 3 to 103, respectively, and the amino acid sequences estimated from the sequences are shown in the sequence number 6 2 to 8 2. 0 C I F activity was measured according to the method shown in Example 13. In addition, the amount of antigen of 0CIF was quantified according to the EIA method described in Example 24. Table 14 shows the comparison results of the activity of the antigen amount unit and the unchanged OCIF. (Please read the notes on the back before filling this page) The paper size printed by the Employees' Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs applies to the Chinese National Standard (CNS) A4 (210X 297 mm) 3 8 0 7 6 538049 A7 B7 V. Description of the invention (68) Table _14 Variation name Active Ministry of Economic Affairs Central Standards Bureau Staff Consumer Cooperatives printed unchanged 0 CIF + 0C IF-C19S + 0C IF-C20S + 0C IF-C21S + 0C IF-C22S + 0C IF-C23S + OCF I-0CR1 00C IF-DCR2 00C IF-DCR3 00C IF-DCR4 COCO IF-DDD1 + 0C IF-DDD2 00C IF-CL + 0C IF-CC + 0C IF-CDD2 + 0C IF-CDD1 + 0C IF-CCR4 00C IF-CCR3 00C IF-CBst + 0 CIF-CS ph + 0C IF-CBsp 00C IF-CPst ((Please read the precautions on the back before filling in this page) Order 4 This paper size applies to Chinese National Standard (CNS) A4 (210X 297 mm) 3 8 0 7 6 68 538049 A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of Invention (6 9) (in the table above, + + Indicates that the activity of the antigen amount unit exceeds 50% of the activity of the unchanged OCIF, + indicates that the above activity is 10% ~ 50%, the activity is less than 10% or the antigen amount cannot be measured correctly). v i) Two-side ink dot analysis The sample 10 / i 1 used for activity measurement will provide western ink dot analysis. 10 / il sample was added 10 / il sample buffer for SDS-PAGE [0.5M Tris-Hcl, 20% glycerol, 4% SDS, 20iug / inl bromophenol blue (PH6.8)], at 1001C Boil for 3 minutes and perform 10% SDS polyacrylamide electrophoresis separation in a non-reduced state. After electrophoretic separation, the protein was dipped in a PVDF membrane (ProBlott®, manufactured by Perkin-Elmer) using a semi-dry immersion device (manufactured by Biorad). After the film was blocked, the EIA described in Example 24 was incubated with a mangosteen peroxo-labeled anti-OCIF antibody at 37 ° C for 2 hours. After washing, the ECL system (Amerskam) was used to test the protein bound to the anti-OCIF antibody. The 0CIF test has about 120kD and 60kD bands. On the other hand, at 0CIF-C23S, OCIF-CL, 0CIF_CC, almost no 60kD band can be detected. In addition, the bands of about 40-50 k D and 30-40 k D were picked out on 0CIF-CDD2 and 0CIF-CDD1 respectively as the main bands. From the above results, it is known that the 380th Cys residue in the amino acid sequence of sequence number 4 in the sequence listing on the 0CIF is related to the formation of the di (poly) form, the haplotype also remains active, and the Asp at 177 値Residue deletions up to the 3rd and 80th Leu can also remain active. [Example 2 3] Some human inductive DNA of 0CIF ^ Isolate T) Some human sweet DHA seed source dust sieve (please read the precautions on the back before filling this page), language β This paper size applies Chinese national standards (CNS) A4 size (210X297 mm) 69 3 8 0 7 6 538049 A7 B7 _____ V. Description of the invention (70) A genomic source library made from Stratagene company using human lung chromosomal DNA and λ PI × ΙΙ vector was purchased. OCIFcDNA was used as a probe for screening. The above-mentioned screening method is basically performed according to the instructions attached to the genomic source bank, but the general methods of manipulating bacteriophage, coliform, DNA, etc. are implemented according to the methods described in the Malecular Cloning: A Laboratory Manual—Book. Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling this page) After checking the titer of the purchased genomic DNA source bank, infect the large intestine with! X106 pfu phage. And seed it on 20 plates (9x 13c «i) with 9ml of top agarose on each plate. After overnight incubation at 371C, Hybond-N nylon membrane (manufactured by Aroersham) was placed on an agarose plate and phages were transcribed. Phage transcribed nylon membrane was placed on filter paper wetted with 1.5M sodium chloride / 0.5M sodium hydroxide solution for one minute, and then treated with 1M Tris-Hcl ((> Η7,5) and 1.5M chlorine, respectively. Sodium chloride / 0.5M Tris-Hcl (pH 7.5) was separately treated for one minute, neutralized, and finally transferred to filter paper moistened with 2XSSC. The nylon membrane was then irradiated with 1200 microjoules (fflicrojoule) of ultraviolet light (UV) using a StratLinker (manufactured by Stratagene) to fix the phage DNA to the membrane. Next, the membrane was dipped in a rapid hybridization buffer (manufactured by Amersham) to perform a pre-hybridization treatment. After one-hour pre-hybridization treatment, OCIFcDNA labeled with 32P was added, and hybridization treatment was performed at 65 ° C overnight. The c DNA probe was a plasmid pBKOCIF having a 1.6 kb OCIFcDHA obtained in Example 11, and was cut with restriction enzymes BamHI and Zhol. The 0CIP cDNA was separated by agarose gel electrophoresis, and the 0CIFcDNM ^ was labeled with Megprime DNA. Articles (products of Aroersham Company) label 32P and the paper size applies to Chinese National Standard (CNS) A4 size (210x297 mm) 7 0 3 8 0 7 6 538049 A7 B7 V. Description of invention (7 1) Central standard of the Ministry of Economic Affairs Printed by the Bureau's Consumer Cooperative (please read the precautions on the back before filling this page). Marking is carried out according to the instructions in the attached note system. For hybridization, approximately 5xl05cpro probe was used per 1ml of hybridization buffer. After hybridization, the nylon membrane was washed with 2XSSS at room temperature for 5 minutes. Then wash four times at 65 ° C with 0,5XSSC / 0.1% SDS for 20 minutes. After washing for the fourth time, the nylon film was dried, and an X-ray film made of Fujifilm Corporation, SU per-HR-Η and a super-sensitive screen were used to perform autoradiography at ~ 80 ° C. . Six messages were examined on the autoradiogram. Therefore, the above agarose was cut out on an agarose plate corresponding to the message, immersed in 0.5 ml SM buffer containing 1% chloroform and left overnight, and phages were extracted. Dilute each phage extract to 1000 times with SM buffer, and then take 1 / i 1 and 20 w 1 of them, re-infect the above coliform, and seed them on the agarose plate with the above agarose according to the above method. on. After the phage is transcribed on the nylon membrane, pre-hybridization, hybridization, washing, drying, and autoradiation are performed according to the method described above. The operation of purifying the phage described above was performed on all the six information parts previously detected on the autoradiogram, and the operation was repeated until all phage spots and cDNA probes were hybridized on the agarose plate. The purified phage spots were excised, immersed in 0.5 ml of SM buffer containing 1% chloroform, and stored at 4 ° C. Based on this, 6 kinds of purified phages were obtained, named 0IF3, A0IF8, A0IF9, AOIFll, A0IF12, A0IF17.

O τ η 由限制酯消化和南方墨點雜化作用所成人類o c τ f某因組DH A純種备之分析按照 Malecular Cioning: A Laboratory Manual—書本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 71 3 8 0 7 6 538049 A7 -- B7 五、發明説明（7 2 ) 11所記載之板溶胞作用方法，將上述純化的6種噬菌體 DNA精製之。將這些DNA用限制酶消化，所得片段用瓊脂糖胃$法分離之。另外，將瓊脂糖凝膠所分離的蛋白質片段 &〜般方法轉移在尼龍膜上後，使用〇 ^〗F c D N A為探針進行軀點雜化作用。其分析結果，顯示分別純化的6種噬 _體為不同種的純種条。由限制酶消化而得DNA片段之中， ^ & OCIFcDNA能雜化者，在質粒載體上傳代無性繁殖（ Subclone)後，按照下述方法進行塩基序列分析。經濟部中央襟準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) II·!!從甚庆I紺D N A純穂备由限制醮消化所得D N A Η段經傳無袢慜豬為暫粒載鵲和其塩某序列之泱宏將A0IF8DNA用限制_EcoRI和Notl消化，所産生片段以〇·?%瓊脂糖凝膠處理而分離之。再把5.8kb的 EcoRI/Notl片段用QIAEZIH_^取組劑（吉阿研公司製品 )按照隨附指示從凝膠中萃取。將此片段和事前用EcoRI和 Notl切割的 pBlue scriptll SK +載體（Stratagene公司製品）和立行 T4連接酶（Ready-To-Go T4 Ligase, Phermacia 公司製品）按照隨附指示進行連接反應。所得重組體質粒導入C 〇 m p e t e n t D Η 5 〇(大腸_ ( A in e r s h a m公司製品）後，播種在含有50/ig/ml安比西林的瓊脂糖培養基上，選擇在具有質粒的大腸菌。按照上述方法所製作的具有5.8kb EcoRI/Notl片段的重組體質粒命名為PBSG8-5.8。其次，用限制酶Hindlll消化PBSG8-5.8所産生的〇.9kb的DNA片段以瓊脂糖凝_法分離，按照上述方法萃取後，插入在事先用 Hindlll切割的 pBlne script II SK_(Stratagene公司本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 72 3 80 76 538049 A7 經濟部中央標準局員工消費合作社印製 ----- -B7_ _________五、發明説明（73 ) 製品），再按照上述方法進行純種条繁殖。上述具有〇 · 9 k b @ΗίΜΙΙΙ片段的重組體質粒命名為pBS8H0.9。另一方面， ^Ec〇RI消化AOIFll的DNA所産生的6kb, 3.6kb,以及 2 · 6 k b的片段分別加以分離後，按照上述相同方法插入 PBlueScriptiisK +載體並進行純種条繁殖。據此所製作的具有6kb, 3.6kb,和2.6kb的EcoRI片段的重組體質粒，分別命名為 pBSGll-6, pBSGII-3.6, pBSGU-2.6。另外，利用限制酶Hindlll消化pBSGll-6所産生2.2kb, l.lkb, l.〇5kb的三種片段用瓊脂糖凝_電泳法分離，分別插人 i>BluescriptiiSK的Hindlll部位而進行純種条繁殖。上述這些具有2.2kb, l.lkb, 1.05kb的Hindlll片段的重組體質粒分別命名為 PBS6H2.2, PBS6H1. 1, PBS6H1.05。基因組D N A的塩基序列分別使用A B I去氧終端子循環定序立卽反應組劑（Perkin-Elmer公司製品）和373DNA序列条統（ Applied Biosystem公司製品）。按照 Maleculr Cioning:A Labaratory Manual書上所記載方法調製得PBSG8-5.8， PBS8H0.9, pBSGll-6, pBSGll-3.6, pBSGll-2.6, PBS6H2.2, PBS6H1.1, pBS6H 1.05,做為決定塩基序列用模板使用。人類OCIF基因組DNA之塩基序列示於序列表中序列號碼1 0 4和1 0 5。介在於表現序列1 ( E X ο η 1 )和表現序列 (請先閱讀背面之注意事項再填寫本頁) 和 η 在介酸例施實碼號列序中7k 表1· 列有序約 , 大定認決確部已全，未間並之列列序序基基塩塩的示間所核的本紙張尺度適用中國國家標準（CNS ) Α4規格（210X 297公釐） 3 8 0 7 6 538049 A7 B7 五、發明説明（7 4 ) 以ETA法亩最0CIF i ) 調製兔孑抗0CTF杭體經濟部中央標準局員工消費合作社印製以曰本雄性白兔（體重為2.5〜3.0kg,由日本北山拉貝士公司購得）3隻為試驗動物，將200/ig/ml的0CIF以等量的彿羅因特完全佐肋劑（D ί b c 〇公司製品）混合而成乳液，每次linl進行皮下免疫處理。免疫處理每隔一週共進行6 次，在最終免疫處理後第10日進行全採血。從分離而得血清按照下述方法進行抗體之精製。即，以PBS稀釋2倍之抗血清中添加硫酸銨使最終濃度成為40W/V%,在41C下放置一小時後，以8000Xg離心20分鐘，而得沈澱物。該沈澱用少量之P B S溶解，對於P B S在4 υ下透析後，用蛋白質 G -瓊脂糖分離管（Pharmacia公司製品）處理之。用PBS洗淨後，以0.1M塩酸甘胺酸緩衝液（PH3.0)將吸附的免疫球蛋白G溶出後，立刻以1 . 5 Μ Ί> i s - H c 1緩衝液（p Η 8 . 7 )調節成中性。溶出的蛋白質餾分以Ρ Β S透析後，測定波長2 8 0 η πι處的吸光度，計算其濃度（Ε1%}〗.5)。以西洋山葵過氧化酶標記的抗0 C I F抗體，乃使用馬來醯亞胺活化過氧化酶組劑 (比阿士公司製品）製作之。即lmg的精製抗體添加以80/ig 的N-琥珀醯亞胺-S-乙醯硫基乙酸，在室溫下反應30分鐘。再添加5mg的羥基胺去除乙醯基後，將修飾的抗體用聚丙烯醯胺脱塩分離管級分處理。蛋白質餾分用lmg的馬來醯亞胺活化過氣化酶混合，在室溫下反應1小時而得酶標記抗體。O τ η Human oc τ f caused by restricted ester digestion and southern blotting hybridization oc τ f Analysis of a group of DH A pure breeds According to Malecular Cioning: A Laboratory Manual—Book paper size applies Chinese National Standard (CNS) A4 Specifications (210X 297 mm) 71 3 8 0 7 6 538049 A7-B7 V. The plate lysis method described in the description of the invention (7 2) 11 will purify the purified 6 kinds of phage DNA. These DNAs were digested with restriction enzymes, and the resulting fragments were separated by the agarose method. In addition, the protein fragment isolated from the agarose gel was transferred to a nylon membrane, and then spot hybridization was performed using F c D N A as a probe. The results of the analysis showed that the six purified phages were pure species of different species. Among the DNA fragments obtained by digestion with restriction enzymes, those with OCIF cDNA hybridization can be subjected to subclone in a plasmid vector, and then the base sequence analysis can be performed according to the following method. Printed by the Consumer Cooperatives of the Central Government Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling out this page) II. !! From Qingqing I. DNA is pure. DNA prepared by restriction. A0IF8 DNA was digested with restriction_EcoRI and Notl to temporarily load the macromolecule and its sequence. The resulting fragment was isolated by treatment with a 0.1% agarose gel. The 5.8 kb EcoRI / Notl fragment was extracted from the gel using QIAEZIH_ ^ group reagent (product of Ji'an Research Co., Ltd.) according to the attached instructions. This fragment was subjected to a ligation reaction with a pBlue scriptll SK + vector (manufactured by Stratagene) and a T4 ligase (Ready-To-Go T4 Ligase, manufactured by Phermacia) previously cut with EcoRI and Notl. The resulting recombinant plasmid was introduced into Cmpetent D Η 50 (large intestine_ (A inersham)), seeded on an agarose medium containing 50 / ig / ml ampicillin, and selected for coliform with the plasmid. According to the method described above The prepared recombinant plasmid with a 5.8kb EcoRI / Notl fragment was named PBSG8-5.8. Second, the 0.9kb DNA fragment produced by digestion of PBSG8-5.8 with the restriction enzyme Hindlll was isolated by agarose gelation method, according to the method described above. After extraction, insert the pBlne script II SK_ (Stratagene company's paper size that applies to Chinese National Standard (CNS) A4 size (210X 297 mm) before printing with Hindlll) 72 3 80 76 538049 A7 ----- -B7_ __________ V. Description of the invention (73) product), and then propagated according to the above method. The above recombinant plasmid with the 0.9 kb @ ΗίΜΙΙΙ fragment was named pBS8H0.9. Another On the one hand, the 6kb, 3.6kb, and 2.6kb fragments produced by ^ EcoRI digestion of AOIF11 DNA were separated and inserted into PBlueScr in the same way as above. The iptiisK + vector was used to propagate purebred strips. Recombinant plasmids with 6 kb, 3.6 kb, and 2.6 kb EcoRI fragments prepared accordingly were named pBSGll-6, pBSGII-3.6, and pBSGU-2.6. The restriction enzyme Hindlll digested the three fragments of 2.2kb, l.lkb, and 1.05kb produced by pBSGll-6 using agarose gel electrophoresis, and inserted them into the Hindlll site of i & BluescriptiiSK to perform pure-line breeding. Recombinant plasmids with Hindlll fragments of 2.2 kb, l.lkb, and 1.05 kb were named PBS6H2.2, PBS6H1.1, 1, PBS6H1.05. The genomic sequences of the genomic DNA were sequenced using ABI deoxyterminator cycle sequencing, respectively. Group preparation (Perkin-Elmer) and 373 DNA sequence system (Applied Biosystem). PBSG8-5.8, PBS8H0.9, pBSGll-6, pBSGll-3.6 were prepared according to the method described in the Maleculr Cioning: A Labaratory Manual. , pBSGll-2.6, PBS6H2.2, PBS6H1.1, pBS6H 1.05, which are used as templates for determining the base sequence. The base sequence of human OCIF genomic DNA is shown in the sequence listing SEQ ID NOs: 104 and 105. Included in the performance sequence 1 (EX ο η 1) and the performance sequence (please read the notes on the back before filling this page) and η in the sequence example of the implementation code number 7k Table 1. The confirmation is complete, and the paper standards verified by the sequencer are listed in the sequence. The standard of this paper is applicable to the Chinese National Standard (CNS) A4 specification (210X 297 mm). 3 8 0 7 6 538049 A7 B7 V. Description of the invention (7 4) Modified rabbits with ETA method 0CIF i) Anti-0CTF printed by male consumer rabbits of the Central Standards Bureau of Hangzhou Municipal Ministry of Economics and Consumer Cooperatives (weight 2.5 ~ 3.0kg, by Acquired by Kitayama Labex Co., Ltd. in Japan) 3 test animals, mixed 200 / ig / ml of 0CIF with the same amount of Freund's complete rib adjuvant (product of D blc 〇) to make an emulsion, each time Linl was treated subcutaneously. Immunization was performed 6 times every other week, and blood was collected on the 10th day after the final immunization. The sera obtained from the separation were purified by the following method. That is, ammonium sulfate was added to the antiserum diluted twice with PBS to make the final concentration 40 W / V%. After being left at 41C for one hour, it was centrifuged at 8000Xg for 20 minutes to obtain a precipitate. The precipitate was dissolved with a small amount of P B S, and after the P B S was dialyzed at 4 υ, it was treated with a protein G-sepharose separation tube (manufactured by Pharmacia). After washing with PBS, the adsorbed immunoglobulin G was eluted with 0.1 M gallate glycine buffer solution (PH 3.0), and immediately with 1.5 M Ί > is-H c 1 buffer (p Η 8. 7) Adjust to neutral. After the eluted protein fraction was dialyzed with PBS, the absorbance at a wavelength of 280 nm was measured, and its concentration was calculated (E1%). 5). Anti-OCI F antibody labeled with wasabi peroxidase was made using maleimide-activated peroxidase group (Bias). That is, 1 mg of purified antibody was added with 80 / ig of N-succinimide-S-acetamidothioacetic acid and reacted at room temperature for 30 minutes. After 5 mg of hydroxylamine was further added to remove the acetamidine group, the modified antibody was treated with a polypropylene amine dehydration separation tube fraction. The protein fraction was mixed with 1 mg of maleimidine imine-activated gasification enzyme, and reacted at room temperature for 1 hour to obtain an enzyme-labeled antibody.

i η 以三明治型E I A法亩最（1 C T F 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 3 8 0 7 6 (請先閱讀背面之注意事項再填寫本頁) 74 538049 A7 B7 五、發明説明（7 5 ) 96洞孔的微滴定板（MaxciSorp Ifflfflunoplate, Nunc公司製品）的各洞孔中，添加以100/il的免抗0CIF抗體（ 2 u g/m 1 , 50mM碩酸緩衝液（pH9.6))在4°C下靜置一夜，使抗體固化。用P B S調製的2 5 %封阻A c e (雪印乳業公司製品）每洞孔中分別添加3 0 0 y 1 ,在3 7 °C下放置1小時加以封阻後，添加檢體（1 0 0 /i 1 /洞孔）在室溫下反應2小時。以含有0.05%1'^6〇20的？85(?831')洗淨3次後，再以稀釋 10000倍的西洋山葵過氧化酶標記抗0CIF抗體各添加 100 μ I ,然後在室溫下培養2小時。用PBST洗淨3次後，加入100yl的酵素基質溶液（TMB, ScyTek公司製品），在室溫下顯色後停止反應。利用微讀譜儀（Ifflinunoreader, HJ2000型，日本Intermed公司製品）測定波長450ηιπ處的吸光度，以精製重組型0 C I F為標準所製校準曲線求得檢體的 0 C I F濃度之定量值。上述0 C I F之校準曲線示於第1 3圖。 [實施例25] 杭niMFM姝杭體 1 ) 人額Π C T F抗體牛産用融合瘤夕謳製經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) 培養人類纖維母細胞I MR-90，由其培養液按照實施例 11中所記載方法精製0 C I F。用P B S溶解精製0 C I F使成為 l〇Ml/l〇〇/il濃度，再將該溶液每隔2星期按照BALB/C条鼠做腹腔内投與而加以免疫處理。第一次和第二次免疫時，投與等量的佛羅因特完全佐助劑。最終免疫後第3日摘取脾臓，分離B淋巴球，按照一般常用的聚乙二醇法和鼠骨髄細胞瘤P3X63-AG8.653進行細胞融合。繼之，為選擇本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 7 5 3 8 0 7 6 538049 A7 B7 經濟部中央標準局員工消費合作社印製五、發明説明（76 ) 融合細胞，在HAT培養基進行培養而篩選融合瘤細胞。其次，為確知所篩選得細胞是否産生0CIF特異性抗體，將 1 0 0 u 1溶解在0 . 1 Μ碳酸氫鈉溶液的1 0 w g / m 1濃度的0 C I F溶液，加入96洞孔的微穴盤（Nunc公司製品），使用所製作的固相E L I S A ,進行融合瘤培養液中的0 C I F特異性抗體之測定。確認有生産抗體的融合瘤用極限稀釋法重複進行3〜5 次純種条繁殖，每次均使用上述ELISA檢查抗體産量。從所得抗體生産株中選擇抗體産量最高純種条株。 ΐ i ) 簠株杭體^生産實施例2 5 - i )項中所得抗體生産株，分別以1 X 1 〇 6量移植在事先用十八碳院（Pristane, Adlorick Chemical公司製品）接種的BALB/C糸鼠之腹腔内。移植2星期後，採取蓄積的腹水，獲得含有本發明的單株抗體的腹水。從該腹水利用親和性凝膠蛋白質A瓊脂糖（B i 〇 - r a d公司製品）進行親和性層析而得到精製抗體。即，用等量的結合緩衝液（Bioiad公司製品）稀釋腹水，吸附在蛋白質A分離管後，用充分量的相同緩衝液洗淨之。I g G以洗提緩衝液（ B i 〇 - r a d公司製品）溶出。所得溶出液以水透析後，進行凍結乾燥。所得精製抗體以S D S - P A G E進行檢驗純度，結果在大約150,000的分子量處確認均一的波帶。 η i )籂潠的0 C I F具有高雜和件的蜇抶杭體溶解實施例2 5 - i i )項中所得抗體於P B S中，依照羅利法進行蛋白質之定量。繼之，利用PBS溶解各抗體使其蛋白濃度為恒定，再藉梯度稀釋法稀釋上述溶液。依照實施 (請先閱讀背面之注意事項再填寫本頁) 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 7 6 3 8 0 7 6 538049 A7 B7 五、發明説明（77 ) 例2 5 - i i )項所記載之固相E L I S A法，篩選能和0 C I F反應到高稀釋條件的單株抗體。結果獲得AIG5, E3H8以及D2F4之三種抗體。 i v ) 抗體次鈒檢驗實施例2 5 - ί i i )所篩選得本發明抗體之主級和次級者，使用免疫球蛋白级和次級分析組劑（Amersham公司製品）加以檢驗之。檢驗方法依照組劑隨附指示實施。其結果示於表 15。 E3H8, AIG5以及 D2F4分別為 IgGi, IgG2a,以及 I g Q 2 b 〇差 15 抗體名稱 I g G 1 I g G 2 a I g G 2 b I g G 3 I g A I g M k A IG5 E3H8 D2F4 一一 + — 一鐵 + (請先閱讀背面之注意事項再填寫本頁) 經濟部中央標準局員工消費合作社印製 v ) 用E L I S A湖丨宙0 C I F之方法將實施例25-iv)項中所得AIG5, E3H8,以及D2F4的三種單株抗體分別做成固相抗體和標記抗體。藉各個組合排列而構築三明治型E L I S A。抗體之標記使用馬來醯亞胺活化過氧化酶（比阿士公司製品）而進行。用0 . 1 Μ的磺酸氫鈉溶液溶解各個抗體成為1 〇 /i g / m ]濃度，按照每洞孔1 0 0 α 1 量分別注入9 6洞孔免疫型穴盤中（N u n c公司製品），在室溫本紙張尺度適用中國國家標準（CNS ) Α4規格（210 X 297公釐） 77 3 8 0 7 6 538049 A7 經濟部中央標準局員工消費合作社印製 B7五、發明説明（78 ) 下放置一夜。繼之，使用1 / 2濃度的封阻愛司液（雪印乳業公司製品）將各穴盤封阻，以含有0.1% TVeen20的PBS (洗淨用緩衝液）洗滌3次。使用第一次反應緩衝劑（含1 / 2 . 5 濃度之封阻愛司液和0.1% Tweer20的0.2M Tris-Hcl緩衝液，pH 7. 4)調製各種濃度的0C IF。將調製好的各種濃度 0 C I F溶液在每洞孔中加入1 0 0 w 1 , 3 7 °C下放置3小時，繼之，利用洗淨緩衝液洗淨3次。稀釋標記抗體使用第二次反應緩衝液（含有1/4濃度的封阻愛司液以及0. 1 % Tween20 的 0.1M Tris-Hcl)緩衝液，ρΗ7·4)。使用第二次反應緩衝液將各標記抗體稀釋成為40 0倍，將各100//1分別注入穴盤各洞孔中。在3 7 υ下放置2小時，然後洗淨3 次後，將l〇〇/il的基質溶液（含有〇.4mg/ml鄰-苯二胺塩酸塩，0 . 0 0 6 %過氧化氫的0 . 1 Μ檸檬酸-磷酸緩衝液，p Η 4，5 ) 添加在穴盤各洞孔中，在3 7 °C下放置於暗室1 5分鐘後，各洞孔中再添加5 0 /i 1的6 N硫酸而終止酵素反應，使用免疫讀譜儀（Imiounoreader, NJ2000型，日本 Interied公司製品）測定波長49 2 n in處的吸光度。以3種抗體分別做成固相抗體或標記抗體的任何組合都獲得良好的測定結果，並確認3種抗體分別為不同抗原決定部位U P i t Ρ e )的0 C I F所成。舉以A I G 5為固相抗體而E 3 Η 8為標記抗體做為例舉時之校準曲線示於第14圖中。 ν i )人類ifn清中的0 C T F夕測宙依據實施例2 5 - v )項之第1 4圖之E L I S A条統，測定5名正常健康人血清中之0CIF。詳言之，按照實施例25-v)項 (請先閱讀背面之注意事項再填寫本頁) 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 7 8 3 8 0 7 6 經濟部中央標準局員工消費合作社印製 538049 A7 B7 五、發明説明（7 9 ) 所示相同方法，將AIG5固定在免疫板（ImmunopUte)上，加入5 0 α 1的人類血清，在3 7 °C下放置3小時。用洗淨緩衝液洗淨3次後，以第二次反應緩衝液稀釋4 0 0倍的E 3 Η 8 標記抗體1 0 0 w 1加入各洞孔中，在3 7 °C下放置2小時。穴盤用洗淨緩衝液洗淨3次後，將上述1 0 0 y 1的基質溶液分別添加到各洞孔中，在3 7 υ下反應1 5分鐘。各洞孔中添加 50//1的6Ν硫酸而終止酵素反應，利用免疫讀譜儀（ Immunoreader)測定波長492nm之吸光度。就含有已知量 0CIF的第一次反薩緩衝液也進行同樣操作，製成如第14圖所示0CIF的校準曲線，由血清試料之吸光度求得血清中的 0CIF量。其結果示於表16。寿_16 血清試料 0CIF量（ng/ml) 1 5 . 0 2 2.0 3 1 . 0 4 3 . 0 5 1 . 5 [實施例2 6 ] 親於骨皙疏鬆症夕治療效果以經切除神經的不動性骨質萎縮病例確認〇 C I F之治療 (請先閱讀背面之注意事項再填寫本頁) 訂本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 79 3 8 0 7 6 538049 A7 B7 經濟部中央標準局員工消費合作社印製五、發明説明 :8 0 ) 1 | 效果〇使用 F ί s C he r条雄性鼠為試驗動物， 6 週齡（體重約 1 I 1 2 0 g )時，由切除左上腕神經叢，造成左前肢無法移動而 1 1 1 成為骨質萎縮病例〇 0C IF用含有0 · 0 1 ^ T w e e η 20的 PBS (-) 1 I 請 I I 調整 9 白翌曰起分別以 5 JL δ /k g 和 5 0 // g /k g用量每隔1 2小先閱 1 I 讀 1 I 時每曰 2 次繼續 2 星期進行靜脈内連曰投與〇正常群施背 1 I 之 1 以假開刀 9 對昭八、、群投與含有 0 . 01 % Twee r20的 PBS (~ ) 0 投注意 1 I 1 I 與終了後摘出左上腕測定其骨質強度。其結果示於第 15 圖項再 1 % 中 0 填寫本頁 1 由上述試驗結果 > 觀察得對照群較之正常群顯示骨質 1 I 強度降低 9 但在 0C IF 5 0 /i g /k g投與群確認有改善效果。 1 1 库業 h 之用可行件 1 1 本發明可提供具有破骨細胞形成抑制活性的新穎蛋白訂 1 質和其有效的製造方法 0 本發明的蛋白質具有破骨細胞形 1 I 成抑制活性 5 可應用在骨質疏鬆症等各種骨量減少性疾病 1 I 之治療劑或 IE 些病患之免疫學診斷用抗原等用途 0 4 1 徹牛物寄託有關事項寄託保存機構之名稱和地址 1 1 名稱：曰本通商産業省工業技術院生命工學工業技 1 1 術研究所 1 1 地址：曰本國茨城縣筑城縣筑波市東一丁巨一番 3 號 1 | (郵遞號碼3 0 5 ) 1 I 保存機構寄託曰期 1 1 I 1 9 9 5 年 6 月 21 曰 (原寄託日期） 1 I I (1 9 9 5 年 6 月2 1曰原寄託單位據微工研菌寄字 1 1 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 80 3 8 0 7 6 538049 A7 B7 五、發明説明（82 ) 序列型：胺基酸局部解剖狀：直鏈狀序列種類：胜肽（蛋白質之内部胺基酸）序列： Z a a lie Arg Phe Leu His Ser Phe Thr 1 5i η Sandwich-type EIA method (1 CTF This paper size applies to Chinese National Standard (CNS) A4 specifications (210X 297 mm) 3 8 0 7 6 (Please read the precautions on the back before filling out this page) 74 538049 A7 B7 5. Description of the invention (7 5) 100 / il anti-0CIF antibody (2 ug / m 1, 50mM master) was added to each well of a 96-well microtiter plate (MaxciSorp Ifflfflunoplate, manufactured by Nunc). Acid buffer (pH 9.6)) was left to stand at 4 ° C overnight to cure the antibody. 25% blocked Ace (made by Xueyin Dairy Co., Ltd.) prepared with PBS was added to each hole 3 0 0 y 1 After blocking at 37 ° C for 1 hour, add a specimen (100 / i 1 / hole) and react at room temperature for 2 hours. (? 831 ') After washing 3 times, add 100 μl each of wasabi peroxidase-labeled anti-OCIF antibody diluted 10,000 times, and then culture at room temperature for 2 hours. After washing 3 times with PBST, add 100yl enzyme substrate solution (TMB, manufactured by ScyTek), stopped the reaction after color development at room temperature. Using micro-reading spectrometer (Ifflinunoreader, HJ2000 type, The product of this Intermed company) measures the absorbance at a wavelength of 450 ηπ, and uses the calibration curve made of refined recombinant 0 CIF as a standard to obtain the quantitative value of 0 CIF concentration in the specimen. The calibration curve of 0 CIF is shown in Figure 13 [ Example 25] Hang niMFM 姝 Hang body 1) Human head Π CTF antibody Fusion tumor for cattle production Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling this page) Culture human fibers Blast cells I MR-90 were purified from the culture solution according to the method described in Example 11. 0 C I F was dissolved and purified with P B S to a concentration of 10 Ml / 100 / il, and the solution was administered intraperitoneally in accordance with BALB / C mice every 2 weeks to immunize them. For the first and second immunizations, an equivalent amount of Freund's complete adjuvant was administered. On the 3rd day after the final immunization, the spleen scabs were removed, the B lymphocytes were isolated, and cell fusion was performed with rat osteoblastoma P3X63-AG8.653 according to the commonly used polyethylene glycol method. Next, in order to select this paper size, the Chinese National Standard (CNS) A4 specification (210X 297 mm) was applied. 7 5 3 8 0 7 6 538049 A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs. 5. Description of the Invention (76) The fused cells were cultured in HAT medium to screen for fused tumor cells. Second, in order to determine whether the screened cells produced 0CIF-specific antibodies, 100 u 1 was dissolved in a 0.1 M solution of 0.1 wg / m 1 0 CIF in a 0.1 M sodium bicarbonate solution, and added to a 96-well microtiter. A plug (manufactured by Nunc) was used to measure the 0 CIF-specific antibody in the fusion tumor culture medium using the prepared solid-phase ELISA. It was confirmed that the antibody-producing fusion tumor was repeatedly subjected to thoroughbred breeding by limiting dilution method 3 to 5 times, and the above-mentioned ELISA was used to check the antibody production. From the obtained antibody producing strains, pure strains with the highest antibody yield were selected. ΐ i) Bacillus hangiensis ^ Production Example 2 5-i) The antibody producing strains were transplanted into BALB inoculated with Eighteen Carbon Institute (Pristane, Adlorick Chemical Co., Ltd.) in an amount of 1 × 106. / C Mole's abdominal cavity. Two weeks after the transplantation, the accumulated ascites was collected to obtain ascites containing the monoclonal antibody of the present invention. From this ascites, affinity chromatography was performed using affinity gel protein A agarose (B i 0-rad product) to obtain a purified antibody. That is, the ascites was diluted with an equal amount of binding buffer (manufactured by Bioiad), adsorbed on a protein A separation tube, and washed with a sufficient amount of the same buffer. Ig G was eluted with an elution buffer (product of Bio-rad Corporation). The obtained eluate was dialyzed against water and then freeze-dried. The purity of the obtained purified antibody was checked by S D S-P A G E. As a result, a uniform band was confirmed at a molecular weight of about 150,000. η i) 籂潠 0 C I F 蜇抶体 body with high heterogeneity and dissolution The antibody obtained in item 25-i i) of Example 25 was dissolved in P B S, and the protein was quantified according to the Raleigh method. Next, each antibody was dissolved in PBS to make the protein concentration constant, and the solution was diluted by a gradient dilution method. According to the implementation (please read the notes on the back before filling this page) This paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X 297 mm) 7 6 3 8 0 7 6 538049 A7 B7 V. Description of the invention (77) The solid-phase ELISA method described in Example 2 5-ii) was used to screen monoclonal antibodies that could react with 0 CIF to high dilution conditions. As a result, three antibodies of AIG5, E3H8 and D2F4 were obtained. i v) Secondary antibody test Example 2 5-i i) The primary and secondary antibodies of the antibodies of the present invention were screened using immunoglobulin-grade and secondary analysis reagents (manufactured by Amersham). The test method is implemented in accordance with the instructions accompanying the kit. The results are shown in Table 15. E3H8, AIG5, and D2F4 are IgGi, IgG2a, and I g Q 2 b 〇 Difference 15 antibody name I g G 1 I g G 2 a I g G 2 b I g G 3 I g AI g M k A IG5 E3H8 D2F4 One One + — One Iron + (Please read the notes on the back before filling this page) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs v) Use the method of ELISA Lake 丨 Zeo 0 CIF to add the items in Example 25-iv) The obtained three monoclonal antibodies of AIG5, E3H8, and D2F4 were made into solid phase antibodies and labeled antibodies, respectively. A sandwich type E L I S A is constructed by arranging each combination. The antibody was labeled using maleimide-activated peroxidase (product of BIAS). Each antibody was dissolved with a 0.1 M sodium hydrogen sulfonate solution to a concentration of 10 / ig / m], and injected into 96-hole immune-type plugs according to the amount of 100 α 1 per hole (Nunc product). ), This paper size applies Chinese National Standard (CNS) A4 specification (210 X 297 mm) at room temperature 77 3 8 0 7 6 538049 A7 Printed by the Consumers Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs B7 V. Invention Description (78) Place overnight. Next, each plug was blocked with a blocking Ais solution (product of Xueyin Dairy Co., Ltd.) at a concentration of 1/2, and washed three times with PBS (washing buffer) containing 0.1% TVeen20. The first reaction buffer (0.2M Tris-Hcl buffer containing 0.1% Tweer20 and 0.1% Tweer20, pH 7.4) was used to prepare 0C IF at various concentrations. Add the prepared 0 C I F solutions of various concentrations to each hole, add 100 w 1, and leave at 3 7 ° C for 3 hours, and then wash them 3 times with washing buffer. Dilute the labeled antibody with a second reaction buffer (0.1M Tris-Hcl containing 0.1% Tween20 blocking buffer) (pH 7.4). Each labeled antibody was diluted to a factor of 400 using a second reaction buffer, and each 100 // 1 was injected into each hole of the plug tray. After standing at 37 for 2 hours, and then washing 3 times, a 100 / il matrix solution (containing 0.4 mg / ml of o-phenylenediamine sulfonium acid, 0.06% of hydrogen peroxide 0.1 μM citric acid-phosphate buffer, p Η 4,5) was added to each hole in the tray, and placed in a dark room at 37 ° C for 15 minutes, and then added to each hole 50 / i The 6 N sulfuric acid of 1 was used to terminate the enzyme reaction, and the absorbance at a wavelength of 49 2 n in was measured using an immunological spectrometer (Imiounoreader, NJ2000 type, manufactured by Interied, Japan). Good results were obtained by using the three antibodies as solid-phase antibodies or any combination of labeled antibodies, and it was confirmed that the three antibodies were formed by 0 C I F of different epitopes (U P i t P e). The calibration curve when A I G 5 is the solid phase antibody and E 3 Η 8 is the labeled antibody is taken as an example. ν i) 0 C T F in the human ifn clear Test the 0 CIF in the serum of 5 normal healthy people according to the E L I S A system in Figure 14 of item 2 5-v). In detail, according to Example 25-v) (please read the precautions on the back before filling this page) This paper size applies the Chinese National Standard (CNS) A4 specification (210X 297 mm) 7 8 3 8 0 7 6 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 538049 A7 B7 5. In the same way as described in the description of the invention (7 9), AIG5 was immobilized on the immune plate (ImmunopUte), and human serum of 0 0 α 1 was added at 37 ° Leave at C for 3 hours. After washing 3 times with washing buffer, dilute 400 times E 3 Η 8 labeled antibody 100 w 1 with the second reaction buffer and add it to each well, and leave it at 37 ° C for 2 hours. . After washing the dish 3 times with washing buffer, the above 100 y 1 matrix solution was added to each well and reacted for 15 minutes at 37 υ. 50 // 1 6N sulfuric acid was added to each well to terminate the enzyme reaction, and the absorbance at a wavelength of 492 nm was measured using an immunoreader (Immunoreader). The same operation was performed for the first anti-Sax buffer containing a known amount of 0CIF, and a calibration curve of 0CIF as shown in Fig. 14 was prepared. The amount of 0CIF in serum was obtained from the absorbance of the serum sample. The results are shown in Table 16. Shou_16 Serum sample 0CIF amount (ng / ml) 1 5. 0 2 2.0 3 1. 0 4 3. 0 5 1. 5 [Example 2 6] The effect of treatment for osteoporosis is to remove the nerve Confirmation of cases of immobile osteopenia 〇 CIF treatment (please read the precautions on the back before filling this page) The size of the paper is applicable to China National Standard (CNS) A4 (210X 297 mm) 79 3 8 0 7 6 538049 A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs. 5. Description of the invention: 8 0) 1 | Effect 〇 Use F s C he r male rats as experimental animals, 6 weeks of age (about 1 I 1 2 0 g) When the left upper carpal plexus was removed, the left forelimb could not move and 1 1 1 became a bone atrophy case. 0C IF was used with PBS containing 0 · 0 1 ^ T wee η 20 (-) 1 I Please adjust II Start with 5 JL δ / kg and 5 0 // g / kg. Dosage every 12 hours 1 I read 1 I read 2 times every 2 days to continue intravenous administration for 0 weeks normal group administration 1 I The first one is to use a sham operation for 9 pairs of Zhao Ba, Qiao and PBS with 0.01% Twee r20 (~). The results are shown in the 15th item and 1%. 0 Fill out this page. 1 From the above test results, it is observed that the control group showed a decrease in bone strength of 1 compared with the normal group, but the intensity was reduced by 9 but administered at 0C IF 5 0 / ig / kg. The group confirmed the improvement effect. 1 1 Possible items for use in the library industry 1 1 The present invention can provide a novel protein 1 with osteoclast formation inhibitory activity and its effective manufacturing method 0 The protein of the present invention has osteoclast shape 1 I inhibitory activity 5 It can be used in various osteoporosis diseases such as osteoporosis. 1 It is a therapeutic agent of I or an antigen for immunological diagnosis of some patients with IE. 0 4 1 The name and address of the depositary institution 1 1 : Yueben Institute of Industrial Technology, Institute of Industrial Technology, Ministry of International Trade and Industry, 1 1 Institute of Technology, 1 1 Address: No. 3, Higashi-ichi, Ikichi, Tsukuba, Tsukoshi, Ibaraki Prefecture, Ibaraki, Japan 1 | (Post No. 3 0 5) 1 I Save Institutional date of deposit 1 1 I 1 9 9 June 21 (the original date of entrustment) 1 II (June 2 1959 1 1 Support unit according to the micro-engineering research bacteria 1 1 This paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X 297 mm) 80 3 8 0 7 6 538049 A7 B7 V. Description of the invention (82) Sequence type: amine Acid local anatomy: linear sequence type: peptide (internal amino acid of protein) sequence: Z aa lie Arg Phe Leu His Ser Phe Thr 1 5

Met Tyr Lys 10 序列號碼：4 序列長度：380 序列型：胺基酸局部解剖狀：直鏈狀序列種類：蛋白質（0 C I P ;無訊息肽）序列： GIu Thr Phe Pro Pro Lys Tyr Leu His Tyr Asp Gla Glu Thr Ser 1 5 10 15Met Tyr Lys 10 sequence number: 4 sequence length: 380 sequence type: amino acid local anatomy: linear sequence type: protein (0 CIP; no message peptide) sequence: GIu Thr Phe Pro Pro Lys Tyr Leu His Tyr Asp Gla Glu Thr Ser 1 5 10 15

His Gln Lea Leu Cys Asp Lys Cys Pro Pro Gly Thr Tyr Leu Lys 20 25 30 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁)His Gln Lea Leu Cys Asp Lys Cys Pro Pro Gly Thr Tyr Leu Lys 20 25 30 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (Please read the precautions on the back before filling this page)

Gin H i s Cys Thr Ala Lys Trp Lys Thr Va1 Cys A la Pro Cyz Pro 35 40 45Gin H i s Cys Thr Ala Lys Trp Lys Thr Va1 Cys A la Pro Cyz Pro 35 40 45

Asp His Tyr Tyr Thr Asp Ser Trp His Thr Ser Asp Glu Cys Leu 50 55 60Asp His Tyr Tyr Thr Asp Ser Trp His Thr Ser Asp Glu Cys Leu 50 55 60

Tyr Cys Ser Pro Val Cys Lys Glu Leu Gin Tyr Val Lys G ίn Glu 65 70 75Tyr Cys Ser Pro Val Cys Lys Glu Leu Gin Tyr Val Lys G ίn Glu 65 70 75

Cys Asa Arg Thr His Asn Arg Val Cys Glu Cys Lys Gla Gly Arg 80 85 . 90 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 82 3 8 0 7 6 538〇49 經濟部中標準員工消費合作社印製 A7 B7 五、發明説明（ο ) 1 ! Tyr Leu Glu lie Glu Phe Cys Leu Lys His Arg Ser Cys Pro Pro 1 I 95 100 105 1 1 Gly Phe Giy Vai Vai Gin Ala Gly Thr Pro Glu Arg Asn Thr Vai 1 I 110 115 120 ，~、請 1 1 I Cys Lys Arg Cys Pro /\sp Giy Phe Phe Ser Asn Glu Thr Ser Ser 先閱 1 I 125 130 135 η 背 ft 1 I Lys Ala Pro Cys Arg Lys His Thr Asn Cys Ser Vai Phe Gly Leu 之注 1 1 140 145 150 意事項 1 Leu Leu Thr Gin Lys Gly Asn Ala Thr His Asp Asn i le Cys Ser 再填 % 1 155 160 165 馬本頁 Gly Asn Ser Glu Ser Thr Gin Lys Cys Gly I le Asp Va 1 Thr Leu 、， 1 1 170 175 180 1 1 Cys Glu Glu Ala Phe Phe Arg Phe Ala Vai Pro Thr Lys Phe Thr 1 I 135 190 195 1 訂 Pro Asn Trp Leu Ser Vai Leu Vai Asp Asn Leu Pro Gly Thr Lys 1 I 200 205 210 1 1 Vai Asn Ala Glu Ser Vai Glu Arg He Lys Arg Gin His Ser Ser 1 | Gin Glu Gin Thr 215 Phe Gin Leu Leu Lys 220 Leu Trp Lys Hl5 Gin 225 Asn 4 1 230 235 240 1 I Lys Asp Gin Asp lie Vai Lys Lys [le [le Gin Asp He Asp Leu 1 1 245 250 255 1 I Cys Glu Asn Ser Vai Gin Arg His Me Gly His Ala Asn Leu Thr 1 1 260 265 270 1 I Phe Glu Gin Leu Arg Ser Lea Met Glu Ser Leu Pro Giy Lys Lys 1 1 275 280 285 1 I Vai Gly Ala Gia Asp [le Glu Lys Thr lie Lys Ala Cys Lys Pro 1 I 290 295 300 1 1 1 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 83 3 8 0 7 6 ^^8〇49Cys Asa Arg Thr His Asn Arg Val Cys Glu Cys Lys Gla Gly Arg 80 85. 90 This paper size applies to China National Standard (CNS) A4 (210X 297 mm) 82 3 8 0 7 6 538〇49 Standard in the Ministry of Economic Affairs Printed by employee consumer cooperative A7 B7 V. Description of invention (ο) 1! Tyr Leu Glu lie Glu Phe Cys Leu Lys His Arg Ser Cys Pro Pro 1 I 95 100 105 1 1 Gly Phe Giy Vai Vai Gin Ala Gly Thr Pro Glu Arg Asn Thr Vai 1 I 110 115 120 ～, please 1 1 I Cys Lys Arg Cys Pro / \ sp Giy Phe Phe Ser Asn Glu Thr Ser Ser Read 1 I 125 130 135 η Back ft 1 I Lys Ala Pro Cys Arg Lys His Thr Asn Cys Ser Vai Phe Gly Leu Note 1 1 140 145 150 Notes 1 Leu Leu Thr Gin Lys Gly Asn Ala Thr His Asp Asn i le Cys Ser Refill% 1 155 160 165 Flyer Gly Asn Ser Glu Ser Thr Gin Lys Cys Gly I le Asp Va 1 Thr Leu ,, 1 1 170 175 180 1 1 Cys Glu Glu Ala Phe Phe Arg Phe Ala Vai Pro Thr Lys Phe Thr 1 I 135 190 195 1 Order Pro Asn Trp Leu Ser Vai Leu Vai Asp Asn Leu Pro Gly Thr Lys 1 I 200 205 210 1 1 Vai Asn Ala Glu Ser Vai Glu Arg He Lys Arg Gin His Ser Ser 1 | Gin Glu Gin Thr 215 Phe Gin Leu Leu Lys 220 Leu Trp Lys Hl5 Gin 225 Asn 4 1 230 235 240 1 I Lys Asp Gin Asp lie Vai Lys Lys [le [le Gin Asp He Asp Leu 1 1 245 250 255 1 I Cys Glu Asn Ser Vai Gin Arg His Me Gly His Ala Asn Leu Thr 1 1 260 265 270 1 I Phe Glu Gin Leu Arg Ser Lea Met Glu Ser Leu Pro Giy Lys Lys 1 1 275 280 285 1 I Vai Gly Ala Gia Asp [le Glu Lys Thr lie Lys Ala Cys Lys Pro 1 I 290 295 300 1 1 1 This paper size applies to China National Standard (CNS) A4 (210X297 mm) 83 3 8 0 7 6 ^^ 8〇49

經濟部中央標準局員工消費合作社印製五、發明説明(8 4 ) ^er Asp Gin lie Leu Lys Leu Leu Ser Leu Trp Arg lie Lys Asn 305 310 315 Asp Gin Asp Thr Leu Lys Gly Leu Met H15 Ala Leu Lys His 320 325 330 ^er Lys Thr Tyr His Phe Pro Lys Thr Val Thr Gin Ser Lea Lys 335 340 345 Thr lie Arg Phe Leu His Ser Phe Thr Met Tyr Lys Lea Tyr 350 355 360 Lys Leu Phe Leu Gla Met lie Gly Asn Gin Vfal Gin Ser Val 365 370 375 Lys [ le Ser Cys Leu ' 380 序列號碼：5 序列長度：401 序列型：胺基酸局部解剖狀：直鏈狀序列種類：蛋白質（0 C I F ;包括訊息肽）序列： Met Asri Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -10 He Lys Trp Thr Thr Gin Gla Thr Phe Pro Pro Lys Tyr Lea His -5 -L 1 5 Tyr Asp Glu Gla Thr Ser His Gin Leu Lea Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Lea Lys Gla His Cys Thr Ala Lys Trp Lys Thr 25 30 35 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 84 3 80 7 6 (、請先閱讀背面之注意事項再填寫本頁) _罐衣· 訂 538049 A7 B7 五、發明説明（85 )Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs. 5. Description of Invention (8 4) ^ er Asp Gin lie Leu Lys Leu Leu Ser Leu Trp Arg lie Lys Asn 305 310 315 Asp Gin Asp Thr Leu Lys Gly Leu Met H15 Ala Leu Lys His 320 325 330 ^ er Lys Thr Tyr His Phe Pro Lys Thr Val Thr Gin Ser Lea Lys 335 340 345 Thr lie Arg Phe Leu His Ser Phe Thr Met Tyr Lys Lea Tyr 350 355 360 Lys Leu Phe Leu Gla Met lie Gly Asn Gin Vfal Gin Ser Val 365 370 375 Lys [le Ser Cys Leu '380 sequence number: 5 sequence length: 401 sequence type: amino acid local anatomy: linear sequence type: protein (0 CIF; including message peptide) sequence: Met Asri Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -10 He Lys Trp Thr Thr Gin Gla Thr Phe Pro Pro Lys Tyr Lea His -5 -L 1 5 Tyr Asp Glu Gla Thr Ser His Gin Leu Lea Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Tyr Lea Lys Gla His Cys Thr Ala Lys Trp Lys Thr 25 30 35 This paper size applies Chinese National Standard (CNS) A4 specifications (210X297 mm) 84 3 80 7 6 (, Please read the note on the back first Items and then Complete this page) _ tanks clothes · Order 538049 A7 B7 V. Description (85 invention)

Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50

Thr Ser Asp Gla Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65Thr Ser Asp Gla Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65

Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80

Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Gla Phe Cys Leu Lys 85 90 95Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Gla Phe Cys Leu Lys 85 90 95

His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Gly Thr 100 105 [[〇His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Gly Thr 100 105 [[〇

Pro Gla Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 115 120 125Pro Gla Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 115 120 125

Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys rtrg Lys His Thr Asn 130 135 140Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys rtrg Lys His Thr Asn 130 135 140

Cys Ser Val Phe Gly Lea Leu Lea Thr Gin Lys Gly Asn Ala Thr 145 150 155Cys Ser Val Phe Gly Lea Leu Lea Thr Gin Lys Gly Asn Ala Thr 145 150 155

His Asp Asa [le Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Cys 160 165 170 G]y lie Asp Val Thr Leu Cys Glu GU Ala Phe Phe Arg Phe Ala 175 180 185 經濟部中央標準局員工消費合作社印製His Asp Asa [le Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Cys 160 165 170 G] y lie Asp Val Thr Leu Cys Glu GU Ala Phe Phe Arg Phe Ala 175 180 185

Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val Leu Val Asp 190 195 200Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val Leu Val Asp 190 195 200

Asn Lea Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg lie 205 210 215Asn Lea Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg lie 205 210 215

Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe Gin Leu Leu Lys 220 225 230Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe Gin Leu Leu Lys 220 225 230

Lea Trp Lys His Gin Asn Lys Asp Gin Asp lie Val Lys Lys lie 235 240 245 3 8 0 7 6 (請先閱讀背面之注意事項再填寫本頁) 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 8 5 A7 B7 、發明説明（8 6 )Lea Trp Lys His Gin Asn Lys Asp Gin Asp lie Val Lys Lys lie 235 240 245 3 8 0 7 6 (Please read the notes on the back before filling out this page) This paper size applies to Chinese National Standard (CNS) A4 specification (210X297 Mm) 8 5 A7 B7, invention description (8 6)

He Gin Asp lie Asp Leu Cys Glu Asn Ser Val Gin Arg His lie 250 255 260He Gin Asp lie Asp Leu Cys Glu Asn Ser Val Gin Arg His lie 250 255 260

Gly His Ala Asn Leu Thr Phe Glu Gin Leu Arg Ser Leu Met Glu (請先閱讀背面之注意事項再填寫本頁) 265 270 275Gly His Ala Asn Leu Thr Phe Glu Gin Leu Arg Ser Leu Met Glu (Please read the notes on the back before filling this page) 265 270 275

Ser Leu Pro Gly Lys Lys Val Gly Ala Glu Asp lie Glu Lys Thr 280 285 290 [le Lys Ala Cys Lys Pro Ser Asp Gin lie Lea Lys Leu Lea Ser 295 300 305Ser Leu Pro Gly Lys Lys Val Gly Ala Glu Asp lie Glu Lys Thr 280 285 290 [le Lys Ala Cys Lys Pro Ser Asp Gin lie Lea Lys Leu Lea Ser 295 300 305

Leu Trp Arg lie Lys Asn Gly Asp Gin rtsp Thr Leu Lys Gly Leu 310 315 320Leu Trp Arg lie Lys Asn Gly Asp Gin rtsp Thr Leu Lys Gly Leu 310 315 320

Met His Ala Leu Lys His Ser Lys Thr Tyr His Phe Pro Lys Thr 3^5 330 335Met His Ala Leu Lys His Ser Lys Thr Tyr His Phe Pro Lys Thr 3 ^ 5 330 335

Val Thr Gin Ser Leu Lys Lys Thr Me Arg Phe Leu His Ser Phe 340 345 350Val Thr Gin Ser Leu Lys Lys Thr Me Arg Phe Leu His Ser Phe 340 345 350

Thr Met Tyr Lys Lea Tyr Gin Lys Leu Phe Leu Glu ilet [le Gly 355 360 365Thr Met Tyr Lys Lea Tyr Gin Lys Leu Phe Leu Glu ilet [le Gly 355 360 365

Asn Gla Val Gin Ser Val Lys lie Ser Cys Lea 370 375 330 經濟部中央標準局員工消費合作社印製序列號碼：6 序列長度：1 2 0 6 序列型：核酸鏈數：1 局部解剖狀：直鏈狀序列種類：cDNA(OCIF) 序列：本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 86 3 8 0 7 6 538049 A7 B7 五、發明説明（87 ) ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 GTTTGCAAAA GATGTCCAGA TGGGTTCTTC TCAAATGAGA CGTCATCTAA AGCACCCTGT 480 AGAAAACACA CAAATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG AAATGCAACA 540 CACGACAACA TATGTTCCGG AAACAGTGAA TCAACTCAAA AATGTGGAAT AGATGTTACC 600 CTGTGTGAGG AGGCATTCTT CAGGTTTGCT GTTCCTACArt AGTTTACGCC TAACTGGCTT 660 AGTGTCTTGG TAGACAATTT GCCTGGCACC AAAGTAAACG CAGAGAGTGT AGAGAGGATA 720 AAACGGCAAC ACAGCTCACA AGAACAGACT TTCCAGCTGC TGAAGTTATG GAAACATCAA 780 AACAAAGACC AAGATATAGT CAAGAAGATC ATCCAAGATA TTGACCTCTG TGAAAACAGC 840 GTGCAGCGGC ACATTGGACA TGCTAACCTC ACCTTCGAGC AGCTTCGTAG CTTGATGGAA 900 AGCTTACCGG GAAAGAAAGT GGGAGCAGAA GACATTGAAA AAACAATAArt GGCATGCAAA 960 CCCAGTGACC AGATCCTGAA GCTGCTCAGT TTGTGGCGAA TAAAAAATGG CGACCAAGAC 1020 ACCTTGAAGG GCCTAATGCA CGCACTAAAG CACTCAAAGA CGTACCACTT TCCCAAAACT 1080 GTCACTCAGA GTCTAAAGAA GACCATCAGG TTCCTTCACA GCTTCACAAT GTACAAATTG 1140 TATCAGAAGT TATTTTTAGA AATGATAGGT AACCAGGTCC AATCAGTAAA AATAAGCTGC L200 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) TTATAA 1206 序列號碼：7 序列長度：1 5 序列型：胺基酸局部解剖狀：直鐽狀序列種類：胜肽（蛋白質之N末端胺基酸）本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 87 3807 6 538049 A7 B7 五、發明説明（88 ) 序列：Asn Gla Val Gin Ser Val Lys lie Ser Cys Lea 370 375 330 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs Serial number: 6 Sequence length: 1 2 0 6 Sequence type: Nucleic acid strand number: 1 Local anatomy: Linear Sequence type: cDNA (OCIF) Sequence: This paper size applies to Chinese National Standard (CNS) A4 specification (210X297 mm) 86 3 8 0 7 6 538049 A7 B7 V. Description of the invention (87) ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 GTTTGCAAAA GATGTCCAGA TGGGTTCTTC TCAAATGAGA CGTCATCTAA AGCACCCTGT 480 AGAAAACACA CAAATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG AAATGCAACA 540 C ACGACAACA TATGTTCCGG AAACAGTGAA TCAACTCAAA AATGTGGAAT AGATGTTACC 600 CTGTGTGAGG AGGCATTCTT CAGGTTTGCT GTTCCTACArt AGTTTACGCC TAACTGGCTT 660 AGTGTCTTGG TAGACAATTT GCCTGGCACC AAAGTAAACG CAGAGAGTGT AGAGAGGATA 720 AAACGGCAAC ACAGCTCACA AGAACAGACT TTCCAGCTGC TGAAGTTATG GAAACATCAA 780 AACAAAGACC AAGATATAGT CAAGAAGATC ATCCAAGATA TTGACCTCTG TGAAAACAGC 840 GTGCAGCGGC ACATTGGACA TGCTAACCTC ACCTTCGAGC AGCTTCGTAG CTTGATGGAA 900 AGCTTACCGG GAAAGAAAGT GGGAGCAGAA GACATTGAAA AAACAATAArt GGCATGCAAA 960 CCCAGTGACC AGATCCTGAA GCTGCTCAGT TTGTGGCGAA TAAAAAATGG CGACCAAGAC 1020 ACCTTGAAGG GCCTAATGCA CGCACTAAAG CACTCAAAGA CGTACCACTT TCCCAAAACT 1080 GTCACTCAGA GTCTAAAGAA GACCATCAGG TTCCTCGTCATCGTCAGCATGC 1T ATC ATCACA TTATAA 1206 Sequence number: 7 Sequence length: 1 5 Sequence type: Amino acid Local anatomy: Mullion Sequence type: Peptide ( N-terminal amino acid of protein) This paper size applies to Chinese National Standard (CNS) A4 (210X297 mm) 87 3807 6 538049 A7 B7 V. Description of the invention (88) Sequence:

Glu Thr Phe Pro Pro Lys Tyr Leu His Tyr Asp Glu Glu Thr Ser 15 10 15 序列號碼：8 序列長度：1185 序列型：核酸鐽數：1 局部解剖狀：直鐽狀序列種類：cDNA(0CIF2) 序列： ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGTGC AATCGCACCC ACAACCGCGT GT.GCGAATGC 300 AAGGAAGGGC GCTACCTTGA GATAGAGTTC TGCTTGAAAC ATAGGAGCTG CCCTCCTGGA 360 TTTGGAGTGG TGCAAGCTGG AACCCCAGAG CGAAATACAG TTTGCAAArtG ATGTCCAGAT 420 GGGTTCTTCT CAAATGAGAC GTCATCTAAA GCACCCTGTA GAAAACACAC AAATTGCAGT 430 經濟部中央標準局員工消費合作社印裂 (請先閱讀背面之注意事項再填寫本頁) GTCTTTGGTC TCCTGCTAAC TCAGAAAGGA AATGCAACAC ACGACAACAT ATGTTCCGGA 540 AACAGTGAAT CAACTCAAAA ATGTGGAATA GATGTTACCC TGTGTGAGGA GGCATTCTTC 600 AGGTTTGCTG TTCCTACAAA GTTTACGCCT AACTGGCTTA GTGTCTTGGT AGACAATTTG 660 CCTGGCACCA AAGTAAACGC AGAGAGTGTA GAGAGGrtTAA AACGGCAACA CAGCl'CACAA 720 GAACAGACTT TCCAGCTGCT GAAGTTATGG AAACATCAAA ACAAAGACCA AGATATAGTC 780 AAGAAGATCA TCCAAGATAT TGACCTCTGT GAAAACAGCG TGGAGCGGCA CATTGGACAT 840 GCTAACCTCA CCTTCGAGCA GCTTCGTAGC TTGATGGAAA GCTTACCGGG AAAGAAAGTG 900 GGAGCAGAAG ACATTGAAAA AACAATAAAG GCATGCAAAC CCAGTGACCA GATCCTGAAG 960 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 88 3 8 0 7 6 538049 A7 B7 經濟部中央標準局員工消費合作社印製五、發明説明（8 9 ) 1 I CTGCTCAGTT TGTGGCGAAT AAAAAATGGC GACCAAGACA CCTTGAAGGG CCTAATGCAC 1020 1 | GCACTAAAGC ACTCAAAGAC GTACCACTTT CCCAAAACTG TCACTCAGAG TCTAAAGAAG 1080 1 I ACCATCAGGT TCCTTCACAG CTTCACAATG TACAAATTGT ATCAGAAGTT ATTTTTAGAA 1140 〆V 1 | ATGATAGGTA ACCAGGTCCA ATCAGTAAAA ATAAGCTGCT TATAA 1185 請先閱讀背面之 1 1 I 序列號碼： 9 1 1 I 序列長度： 394 /王意事 1 1 I 序局列型部解 : 胺基酸析狀：直鏈狀項再填寫本頁 1 % 1 序列種類：蛋白質（0C IF2) 1 I 序列： 1 1 1 Met As η Asn Leu Lea Cys Cys Ala Leu Val Phe Leu Asp I le Ser 1 1 -20 -15 -10 訂 I lie Lys Trp Thr Thr Gin G1 u Thr Phe Pro Pro Lys Tyr Leu His 1 1 -5 1 5 1 I Ty r Asp G1 u G1 u Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 1 1 10 15 20 4 Pro G ly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 1 I 25 30 35 1 1 Val Cys A la Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 1 1 40 45 50 1 1 Thr Ser Asp G t u Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Cys 1 I 00 60 65 1 1 Asn Arg Thr His Asa Arg Vai Cys Glu Cys Lys Glu G ly Arg Tyr 1 I 70 75 80 1 1 I Leu G1 a lie Giu Phe Cys Leu Lys His Arg Ser Cys Pro Pro Gly 1 1 85 90 95 1 1 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 8 g 3 8 0 7 6 五經濟部中央標準局員工消費合作社印製 A7 B7 發明説明（9 0 )Glu Thr Phe Pro Pro Lys Tyr Leu His Tyr Asp Glu Glu Thr Ser 15 10 15 Sequence Number: 8 Sequence Length: 1185 Sequence Type: Nucleic Acid Number: 1 Local Anatomy: Orthogonal Sequence Type: cDNA (0CIF2) Sequence: ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGTGC AATCGCACCC ACAACCGCGT GT.GCGAATGC 300 AAGGAAGGGC GCTACCTTGA GATAGAGTTC TGCTTGAAAC ATAGGAGCTG CCCTCCTGGA 360 TTTGGAGTGG TGCAAGCTGG AACCCCAGAG CGAAATACAG TTTGCAAArtG ATGTCCAGAT 420 GGGTTCTTCT CAAATGAGAC GTCATCTAAA GCACCCTGTA GAAAACACAC AAATTGCAGT 430 Employee Consumer Cooperative Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling out this page) GTCTTTGGTC TCCTGCTAAC TCAGAAAGGA AATGCAACACACGACAACAT ATGTTCCGGAGA GATCACACTGAG 600 AGGTTTGCTG TTCCTACAAA GTTTACGCCT AACTGGCTTA GTGTCTTGGT AGACAATTTG 660 CCTGGCACCA AAGTAAACGC AGAGAGTGTA GAGAGGrtTAA AACGGCAACA CAGCl'CACAA 720 GAACAGACTT TCCAGCTGCT GAAGTTATGG AAACATCAAA ACAAAGACCA AGATATAGTC 780 AAGAAGATCA TCCAAGATAT TGACCTCTGT GAAAACAGCG TGGAGCGGCA CATTGGACAT 840 GCTAACCTCA CCTTCGAGCA GCTTCGTAGC TTGATGGAAA GCTTACCGGG AAAGAAAGTG 900 GGAGCAGAAG ACATTGAAAA AACAATAAAG GCATGCAAAC CCAGTGACCA GATCCTGAAG 960 suitable for the present scale paper China National Standard (CNS) A4 specification (210X 297 mm) 88 3 8 0 7 6 538049 A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (8 9) 1 I CTGCTCAGTT TGTGGCGAAT AAAAAATGGC GACCAAGACA CCTTGAAGGG CCTAATGCAC 1020 1 GCACTAAAGC ACTCAAAGAC GTACCACTTT CCCAAAACTG TCACTCAGAG TCTAAAGAAG 1080 1 I ACCATCAGGT TCCTTCACAG CTTCACAATG TACAAATTGT ATCAGAAGTT ATTTTTAGAA 1140 〆V 1 | ATGATAGGTA ACCAGGTCCA ATCAGTAAAA ATAAGCTGCT I sequence 1 1 1 ATA 1 1 1 Column length: 394 / Wang Yishi 1 1 I Sequence of partial type solution: amino acid precipitation: linear items, fill in this page again 1% 1 Sequence type: protein (0C IF2) 1 I sequence: 1 1 1 Met As η Asn Leu Lea Cys Cys Ala Leu Val Phe Leu Asp I le Ser 1 1 -20 -15 -10 Order I lie Lys Trp Thr Thr Gin G1 u Thr Phe Pro Pro Lys Tyr Leu His 1 1 -5 1 5 1 I Ty r Asp G1 u G1 u Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 1 1 10 15 20 4 Pro G ly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 1 I 25 30 35 1 1 Val Cys A la Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 1 1 40 45 50 1 1 Thr Ser Asp G tu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Cys 1 I 00 60 65 1 1 Asn Arg Thr His Asa Arg Vai Cys Glu Cys Lys Glu G ly Arg Tyr 1 I 70 75 80 1 1 I Leu G1 a lie Giu Phe Cys Leu Lys His Arg Ser Cys Pro Pro Gly 1 1 85 90 95 1 1 This paper size applies to Chinese National Standard (CNS) A4 (210X297 mm) 8 g 3 8 0 7 6 5 Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 Description of Invention (9 0)

Phe Gly Val Val Gin Ala Gly Thr Pro Glu Arg Asn Thr Vai Cys 100 105 110Phe Gly Val Val Gin Ala Gly Thr Pro Glu Arg Asn Thr Vai Cys 100 105 110

Lys Arg Cys Pro Asp Gly Phe Phe Ser Asn Glu Thr Ser Ser Lys 115 120 125Lys Arg Cys Pro Asp Gly Phe Phe Ser Asn Glu Thr Ser Ser Lys 115 120 125

Ala Pro Cys Arg Lys His Thr Asn Cys Ser Val Phe Gly Leu Lea 130 135 · 140Ala Pro Cys Arg Lys His Thr Asn Cys Ser Val Phe Gly Leu Lea 130 135140

Leu Thr Gin Lys Gly Asn Ala Thr His Asp Asn lie Cys Ser Gly 145 150 155Leu Thr Gin Lys Gly Asn Ala Thr His Asp Asn lie Cys Ser Gly 145 150 155

Asn Ser Glu Ser Thr Gin Lys Cys Gly lie Asp Val Thr Leu Cys 160 165 170Asn Ser Glu Ser Thr Gin Lys Cys Gly lie Asp Val Thr Leu Cys 160 165 170

Giu Glu Ala Phe Phe Arg Phe Ala Val Pro Thr Lys Phe Thr Pro 175 L80 185Giu Glu Ala Phe Phe Arg Phe Ala Val Pro Thr Lys Phe Thr Pro 175 L80 185

Asn Trp Leu Ser Val Leu Val Asp Asn Leu Pro Gly Thr Lys. Val 190 195 200Asn Trp Leu Ser Val Leu Val Asp Asn Leu Pro Gly Thr Lys. Val 190 195 200

Asn Ala Giu Ser Val Glu Arg lie Lys Arg Gin His Ser Ser Gin 205 210 215Asn Ala Giu Ser Val Glu Arg lie Lys Arg Gin His Ser Ser Gin 205 210 215

Glu Gin Thr Phe Gin Leu Leu Lys Leu Trp Lys His Gin Asn Lys 220 225 230Glu Gin Thr Phe Gin Leu Leu Lys Leu Trp Lys His Gin Asn Lys 220 225 230

Asp Gin Asp lie Va1 Lys Lys [le [le Gin Asp [le Asp Leu Cys 235 240 245Asp Gin Asp lie Va1 Lys Lys [le [le Gin Asp [le Asp Leu Cys 235 240 245

Glu Asn Ser Val Gin Arg His lie Gly His Ala Asn Leu Thr Phe 250 255 260Glu Asn Ser Val Gin Arg His lie Gly His Ala Asn Leu Thr Phe 250 255 260

Glu Gin Leu Arg Ser Leu !1e t Glu Ser Lea Pro Gly Lys Lys Val 265 270 275Glu Gin Leu Arg Ser Leu! 1e t Glu Ser Lea Pro Gly Lys Lys Val 265 270 275

Gly Ala Glu Asp lie Glu Lys Thr lie Lys Ala Cys Lys Pro Ser 280 285 290Gly Ala Glu Asp lie Glu Lys Thr lie Lys Ala Cys Lys Pro Ser 280 285 290

Asp G ίη Ile Leu Lys Leu Leu Ser Leu Trp Arg He Lys Asn Gly 295 300 305 (請先閱讀背面之注意事項再填寫本頁) 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 90 3 8 0 7 6 經濟部中央標準局員工消費合作社印製 538049 A7 B7 五、發明説明（9 1 )Asp G ίη Ile Leu Lys Leu Leu Ser Leu Trp Arg He Lys Asn Gly 295 300 305 (Please read the precautions on the back before filling out this page) This paper size applies to China National Standard (CNS) A4 (210X297 mm) 90 3 8 0 7 6 Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs 538049 A7 B7 V. Description of Invention (9 1)

Asp Gin Asp Thr Leu Lys Gly Leu Met His Ala Leu Lys His Ser 310 315 320Asp Gin Asp Thr Leu Lys Gly Leu Met His Ala Leu Lys His Ser 310 315 320

Lys Thr Tyr His Phe Pro Lys Thr Val Thr Gin Ser Leu Lys Lys 325 330 335Lys Thr Tyr His Phe Pro Lys Thr Val Thr Gin Ser Leu Lys Lys 325 330 335

Thr He Arg Phe Lea His Ser Phe Thr Met Tyr Lys Leu Tyr Gin 340 345 350Thr He Arg Phe Lea His Ser Phe Thr Met Tyr Lys Leu Tyr Gin 340 345 350

Lys Leu Phe Leu Glu Met lie Gly Asa Gin Val Gin Ser Val Lys 355 360 365 lie Ser Cys Leu 370 序列號碼：1 0 序列長度：1 0 8 9 序列型：核酸鏈數：1 局部解剖狀：直鏈狀序列種類：cDNA(0CIF3) 序列： ATCAACAAGT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60Lys Leu Phe Leu Glu Met lie Gly Asa Gin Val Gin Ser Val Lys 355 360 365 lie Ser Cys Leu 370 sequence number: 1 0 sequence length: 1 0 8 9 sequence type: number of nucleic acid strands: 1 local anatomy: linear Sequence type: cDNA (0CIF3) Sequence: ATCAACAAGT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60

CrtGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GT.ACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAC TGACGAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA ACCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 (請先閱讀背面之注意事項再填寫本頁) Γ 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 9 1 3 8 0 7 6 538049 A7 經濟部中央檩準局員工消費合作衽印製 B7 五、發明説明（92 ) CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 GTTTGCAAAA GATGTCCAGA TGGGTTCTTC TCAAATGAGA CGTCATCTAA AGCACCCTGT 480 AGAAAACACA CAAATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG AAATGCAACA 540 CACGACAACA TATGTTCCGG AAACAGTGAA TCAACTCAAA AATGTGGAAT AGATGTTACC 600 CTGTGTGAGG AGGCATTCTT CAGGTTTGCT GTTCCTACAA AGTTTACGCC TAACTGGCTT 660 AGTGTCTTGG TAGACAATTT GCCTGGCACC AAAGTAAACG CAGAGAGTGT AGAGAGGATA 720 AAACGGCAAC ACAGCTCACA AGAACAGACT TTCCAGCTGC TGAAGTTATG GAAACATCAA 730 AACAAAGACC AAGATATAGT CAAGAAGATC ATCCArtGATA TTGACCTCTG TGAAAACAGC 840 GTGCAGCGGC ACATTGGACA TGCTAACCTC AGTTTGTGGC GAATAAAAAA TGGCGACCAA 900 GACACCTTGA AGGGCCTAAT GCACGCACTA AAGCACTCAA AGACGTACCA CTTTCCCAAA 960 ACTGTCACTC AGAGTCTAAA GAAGACCATC AGGTTCCTTC ACAGCTTCAC AATGTACAAA 1020 TTGTATCAGA AGTTATTTTT AGAAATGATrt GGTAACCAGG TCCAATCAGT AAAAATrtAGC 1080 TGCTTATArt 1089 序列號碼·· 11 序列長度：362 序列型：胺基酸鐽數：1 局部解剖狀：直鏈狀序列種類：蛋白質（0CIF3) 序列： ilet Asa Lys Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu II13 '5 1 5 Tyr Asp Glu Glu Thr Ser His Gin Lea Lea Cys Asp Lys Cys Pro 10 15 20 本紙張尺度適用中國國家標準（CNS ) A4規格（21〇X 297公釐） 92 3 8 0 76 (請先閲讀背面之注意事項再填寫本頁) 訂 d 538〇49CrtGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GT.ACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAC TGACGAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA ACCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 (Read Notes on the back and then fill the page) Γ This paper size is in accordance with Chinese National Standard (CNS) A4 (210X 297 mm) 9 1 3 8 0 7 6 538049 A7 Printed by B7 Consumer Cooperation of the Central Bureau of Standards of the Ministry of Economic Affairs 5. Description of the invention (92) CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 GTTTGCAAAA GATGTCCAGA TGGGTTCTTC TCAAATGAGA CGTCATCTAA AGCACCCTGT 480 AGAAAACACA CAAATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG AAATGCAACA 540 CACGACAACA TATGTTCCGG AAACAGTGAA TCAACTCAAA AATGTGGAAT AGATGTTACC 600 CTGTGTGAGG AGGCATTCTT CAGGTTTGCT GTTCCTACAA AGTTTACGCC TAACTGGCTT 660 AGTGTCTTGG TAGACAATTT GCCTGGCACC AAAGTAAACG CAGAGAGTGT AGAGAGG ATA 720 AAACGGCAAC ACAGCTCACA AGAACAGACT TTCCAGCTGC TGAAGTTATG GAAACATCAA 730 AACAAAGACC AAGATATAGT CAAGAAGATC ATCCArtGATA TTGACCTCTG TGAAAACAGC 840 GTGCAGCGGC ACATTGGACA TGCTAACCTC AGTTTGTGGC GAATAAAAAA TGGCGACCAA 900 GACACCTTGA AGGGCCTAAT GCACGCACTA AAGCACTCAA AGACGTACCA CTTTCCCAAA 960 ACTGTCACTC AGAGTCTAAA GAAGACCATC AGGTTCCTTC ACAGCTTCAC AATGTACAAA 1020 TTGTATCAGA AGTTATTTTT AGAAATGATrt GGTAACCAGG TCCAATCAGT AAAAATrtAGC 1080 TGCTTATArt 1089 ·· sequence number 11 Sequence length: 362 Sequence type: Amino acid number: 1 Local anatomy: Linear sequence type: Protein (0CIF3) Sequence: ilet Asa Lys Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu II13 '5 1 5 Tyr Asp Glu Glu Thr Ser His Gin Lea Lea Cys Asp Lys Cys Pro 10 15 20 This paper size applies to Chinese National Standard (CNS) A4 Specifications (21〇X 297 mm) 92 3 8 0 76 (Please read the notes on the back before filling this page) Order d 538〇49

i、發明説明（93 )i. Description of the invention (93)

Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35

Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His (請先閲讀背面之注意事項再填寫本頁) 40 45 50Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His (Please read the notes on the back before filling this page) 40 45 50

Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65

Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys TO 75 80Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys TO 75 80

Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Lea Lys 85 90 95Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Lea Lys 85 90 95

His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Gly Thr • 100 105 110His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Gly Thr • 100 105 110

Pro Glu Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 115 120 125Pro Glu Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 115 120 125

Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 130 135 140Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 130 135 140

Cys Ser Val Phe Gly Leu Leu Leu Thr Gin Lys Gly Asn Ala Thr 145 150 155Cys Ser Val Phe Gly Leu Leu Leu Thr Gin Lys Gly Asn Ala Thr 145 150 155

His Asp Asn lie Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Cys 160 165 170 經濟部中央榡準局員工消費合作社印製His Asp Asn lie Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Cys 160 165 170

Gly He Asp Val Thr Leu Cys Glu Glu Ala Phe Phe Arg Phe Ala 175 180 185Gly He Asp Val Thr Leu Cys Glu Glu Ala Phe Phe Arg Phe Ala 175 180 185

Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg lie 205 210 215Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg lie 205 210 215

Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe Gin Leu Leu Lys 220 225 230 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 93 3 8 0 7 6 538049 A7 B7 五、發明説明（94 )Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe Gin Leu Leu Lys 220 225 230 This paper size applies to China National Standard (CNS) A4 (210X297 mm) 93 3 8 0 7 6 538049 A7 B7 V. Description of the invention (94 )

Lea Trp Lys His Gin Asn Lys Asp Gin Asp lie Val Lys Lys lie 235 240 245 lie Gin Asp lie Asp Leu Cys Gla Asn Ser Val Gin Arg His lie 250 255 260Lea Trp Lys His Gin Asn Lys Asp Gin Asp lie Val Lys Lys lie 235 240 245 lie Gin Asp lie Asp Leu Cys Gla Asn Ser Val Gin Arg His lie 250 255 260

Gly His Ala Asn Leu Ser Leu Trp Arg lie Lys Asn Gly Asp Gin 265 270 275Gly His Ala Asn Leu Ser Leu Trp Arg lie Lys Asn Gly Asp Gin 265 270 275

Asp Thr Leu Lys Gly Lea Met His Ala Leu Lys His Ser Lys Thr 280 285 290Asp Thr Leu Lys Gly Lea Met His Ala Leu Lys His Ser Lys Thr 280 285 290

Tyr His Phe Pro Lys Thr Val Thr Gin Ser Lea Lys Lys Thr Me 295 300 305Tyr His Phe Pro Lys Thr Val Thr Gin Ser Lea Lys Lys Thr Me 295 300 305

Arg Phe Leu His Ser Phe Thr Met Tyr Lys Lea Tyr Gin Lys Leu 310 315 320Arg Phe Leu His Ser Phe Thr Met Tyr Lys Lea Tyr Gin Lys Leu 310 315 320

Phe Leu Glu Met [le Gly Asn Gin Val Gin Ser Val Lys [le Ser 325 330 335Phe Leu Glu Met [le Gly Asn Gin Val Gin Ser Val Lys [le Ser 325 330 335

Cys Leu 340 經濟部中央標準局員工消費合作社印製 (請先閲讀背面之注意事項再填寫本頁) 序列號碼：1 2 序列長度：465 序列型：核酸鏈數：1 局部解剖狀：直鏈狀序列種類：cDNA(0CIF4) 序列： ATGAACAAGT TGCTGTGCTG CTCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 94 38 0 76 538049 A7 B7 五、發明説明（95 ) TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 24〇 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GTACGTGTCA ATGTGCAGCA 420 ΑΑΑΠΑΑΤΤΑ GGATCATGCA AAGTCAGATA GTTGTGACAG TTTAG 465 序列號碼：1 3 序列長度：1 5 4 序列型：胺基酸鐽數：1 局部解剖狀：直鏈狀序列種類：蛋白質（0CIF4) 序列： fie t Asn Lys Leu Leu Cys Cys Ser Leu Val Phe Leu Asp [le Sec ' -20 -15 -10 [le Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 1 5Cys Leu 340 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling out this page) Sequence Number: 1 2 Sequence Length: 465 Sequence Type: Nucleic Acid Chain: 1 Local Anatomy: Linear Sequence type: cDNA (0CIF4) Sequence: ATGAACAAGT TGCTGTGCTG CTCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 This paper is in accordance with the Chinese National Standard (CNS) A4 specification 5 938 3820 (21038297) Description (95) TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 24〇CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GTACGTGTCA ATGTGCAGCA 420 ΑΑΑΠΑΑΤΤΑ GGATCATGCA AAGTCAGATA GTTGTGACAG TTTAG 465 sequence number: 1 3 Sequence length: 1 5 4 Sequence type: Amino acid number: 1 Local anatomy: linear sequence type: protein (0CIF4) sequence: fie t Asn Lys Leu Leu Cys Cys Ser Leu Val Phe Leu Asp [le Sec '-20 -15 -10 [le Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 1 5

Tyr Asp Glu Cla Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 經濟部中央標準局員工消費合作社印製Tyr Asp Glu Cla Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20

Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 GU Tyr Val Lys GU Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80 3 80 7 6 (請先閲讀背面之注意事項再填寫本頁) 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 538049 A7 B7 經濟部中央標準局員工消費合作社印製五、發明説明（96 ) G1u Cys Lys G1u Gly Arg Tyr Leu G1α Ile Glu Phe Cys Leu Lys 85 90 95 His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Gly Thr 100 105 110 Cys Gla Cys Ala Ala Lys Lea lie Arg lie Met Gin Ser Gin lie 115 120 125 Val Val Thr Val 130 序列號碼：1 4 序列長度：438 序列型：核酸鏈數：1 局部解剖狀：直鏈狀序列種類：cDNA(0CIF5) 序列： ATGAACAAGT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCArtA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GATGCAGGAG AAGACCCAAG 420 CCACAGATAT GTATCTGA 438 序列號碼：1 5 序列長度：1 4 0 序列型：胺基酸 (請先閱讀背面之注意事項再填寫本頁)Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 GU Tyr Val Lys GU Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80 3 80 7 6 (Please read the notes on the back before filling in (This page) This paper size applies to Chinese National Standard (CNS) A4 (210X 297 mm) 538049 A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (96) G1u Cys Lys G1u Gly Arg Tyr Leu G1α Ile Glu Phe Cys Leu Lys 85 90 95 His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Gly Thr 100 105 110 Cys Gla Cys Ala Ala Lys Lea lie Arg lie Met Gin Ser Gin lie 115 120 125 Val Val Thr Val 130 Sequence number: 1 4 Sequence length: 438 Sequence type: Nucleic acid strand number: 1 Local anatomy: Linear sequence type: cDNA (0CIF5) Sequence: ATGAACAAGT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCArtA GTACCTTCAT TATGACGAAG TCCTCTAGArt AAACAACACT GTACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGAC GAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 CATAGGAGCT GCCCTCCT TAG 1 sequence: the sequence of the ATGACCAG: GTGCAAGCTG GATGCAGGAG CCAGAGAG (Fill in this page again)

、1T 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） ⑽ 3 8 0 7 6 538〇49、 1T This paper size is applicable to China National Standard (CNS) A4 (210X297 mm) ⑽ 3 8 0 7 6 538〇49

五、發明説明（9 7 ) _數：！ ^部解剖狀：直鏈狀 $列種類：蛋白質（0CIF5) 序列：V. Description of the invention (9 7) _ number :! ^ Anatomy: straight chain $ Column type: protein (0CIF5) Sequence:

Asn Lys Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10Asn Lys Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10

He Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Lea His *5 1 5He Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Lea His * 5 1 5

Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20

Pro Gly Thr Tyr Lea Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35Pro Gly Thr Tyr Lea Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35

Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Lea 55 60 65Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Lea 55 60 65

Glu Cys Lys Giu Gly Arg Tyr Lea Glu lie Gla Phe Cys Lea Lys 經濟部.中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) 85 90 95Glu Cys Lys Giu Gly Arg Tyr Lea Glu lie Gla Phe Cys Lea Lys Ministry of Economy. Printed by the Consumer Standards Cooperative of the Central Bureau of Standards (Please read the notes on the back before filling out this page) 85 90 95

His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Gly Cys 100 105 110His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Gly Cys 100 105 110

Arg Arg Arg Pro Lys Pro Gin ile Cys lie 115 120 125 序列號碼：1 6 序列長度：20 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 97 3 8 0 7 6 538049 A7 B7 五、發明説明（98 ) 序列型：核酸鏈數：1 局部解剖狀：直鏈狀序列種類：合成DNA(引物T3) 序列： A ATTAACCCT CACTAAAGGG 20 序列號碼：1 7 序列長度：22 序列型：核酸鐽數：1 局部解剖狀：直鏈狀序列種類：合成DNA (引物T7) 序列： GTAATACGAC TCACTATAGG GC 22 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) 序列號碼：1 8 序列長度：20 序列型：核酸鏈數：1 局部解剖狀：直鏈狀序列種類：合成DN A (引物IF 1) 序列： ACATCAAAAC AAAGACCAAG 20 序列號碼：1 9 序列長度：20 本紙張尺度適用中國國家標準（CNS ) A4規格（210 X 297公釐） 98 3 8 0 7 6 538049 A7 B7 五、發明説明（9 9 ) 序列型：核酸鏈數：1 局部解剖狀：直鏈狀序列種類：合成DNA (引物IF2) 序列： TCTTGGTCTT TGTTTTGATG 20 序列號碼：20 序列長度：20 序列型：核酸鏈數：1 局部解剖狀：直鏈狀序列種類··合成D N A (引物I F 3 ) 序列： TTATTCGCCA CAAACTGAGC 20 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) 序列號碼：2 1 序列長度：20 序列型：核酸鏈數：1 局部解剖狀：直鏈狀序列種類：合成DN A (引物IF4) 序列： TTGTGAAGCT GTGAAGGAAC 20 序列號碼：序列長度：20 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 99 3 8 0 7 6 538049 A7 B7 五、發明説明（1 00) 序列型：核酸鏈數：1 局部解剖狀：直鐽狀序列種類：合成DNA(引物IF5) 序列： GCTCAGTTTG TGGCGAATAA 20 序列號碼：23 序列長度：20 序列型：核酸鏈數：1 局部解剖狀：直鏈狀序列種類：合成DNA (引物IF6) 序列： GTGGGAGCAG AAGACATTGA 20 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) 序列號碼：24 序列長度：20 序列型：核酸鏈數：1 局部解剖狀：直鏈狀序列種類：合成DNA (引物IF7) 序列： AATGAACAAC TTGCTGTGCT 20 序列號碼：25 序列長度：20 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 100 3 8 0 7 6 538049 A7 B7 經濟部中央標準局員工消費合作社印製五、發明説明（101) 序列型：核酸鏈數：1 局部解剖狀：直鏈狀序列種數：合成DNA (引物IF8) 序列： TGACAAATGT CCTCCTGGTA 20 序列號碼：26 序列長度：20 序列型：核酸鏈數：1 局部解剖狀：直鏈狀序列種類：合成DN A (引物IF9) 序列： AGGTAGGTAC CAGGAGGACA 20 序列號碼：27 序列長度：20 序列型：核酸鏈數：1 局部解剖狀：直鏈狀序列種類：合成DN A (引物IF 10) 序列： GAGCTGCCCT CCTGGATTTG 20 序列號碼：28 序列長度：20 (請先閱讀背面之注意事項再填寫本頁) ·裝· 、?τ d 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 101 3 8 0 7 6 538049 A7 B7 經濟部中央標準局員工消費合作社印製五、發明説明（102) 1 1 序列型核酸 1 I 鐽數： 1 1 1 I 局部解剖狀 :直鏈狀請 1 1 1 序列種類 * 合成DN Α (引物IF1 1 ) 閱讀背 1 1 序列 * 之注意 1 CAAACTGTAT TTCGCTCTGG 20 1 I 事項再 1 I 序列號碼 : 29 % 序列長度 ♦ 20 填寫本頁 1 序列型 : 核酸、—〆 1 I 鐽數： 1 1 1 1 局部解剖狀 :直鏈狀 1 1 訂序列種類 : 合成DN A (引物IF12) 1 序列； 1 1 GTGTGAGGAG GCATTCTTCA 20 1 | 序列跡 m 碼 : 30 4 序列長度 : 32 1 I 序列型 : 核 •ΤΓ/Λ 酸 1 1 鏈數： 1 1 1 局部解剖狀：直鏈狀 1 1 序列種類合成DNA(引物C19SF) 1 1 序列： 1 I GAATCAACTC AAAAAAGTGG AATAGATGTT AC 32 1 I 序列號碼 ♦· 31 1 1 I 序列長度 * 3 2 1 1 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 102 3 8 0 7 6 538049 A7 B7 經濟部中央標準局員工消費合作社印製五、發明説明（1 0 3) 序列型：核酸鏈數：1 局部解剖狀：直鏈狀序列種類：合成DNA(引物C19SR) 序列： GTAACATCTA TTCCACTTTT TTGAGTTGAT TC 32 序列號碼·· 32 序列長度：30 序列型··核酸鐽數：1 局部解剖狀：直鏈狀序列種類：合成DN A (引物C20SF) 序列： ATAGATGTTA CCCTGAGTGA GGAGGCATTC 30 序列號碼：33 序列長度：30 序列型：核酸鏈數：1 局部解剖狀：直鏈狀序列種類：合成DNA (引物C20SR) 序列： GAATGCCTCC TCACTCAGGG TAACATCTAT 30 序列號碼：34 序列長度：3 1 (請先閱讀背面之注意事項再填寫本頁) 衣. 訂 __· 本紙張尺度適用中國國家標準（CNS ) Α4規格（210X 297公釐） 103 38 0 7 6 538049 A7 B7 經濟部中央標準局員工消費合作社印製五、發明説明（104) 序列型：核酸鏈數：1 局部解剖狀：直鏈狀序列種類：合成D N A (引物C 2 1 S F ) 序列： CAAGATATTG ACCTCAGTGA AAACAGCGTG C 31 序列號碼：35 序列長度：3 1 序列型：核酸鐽數：1 局部解剖狀：直鐽狀序列種類：合成DNA (引物C21SR) 序列： GCACGCTGTT TTCACTGAGG TCAATATCTT G 31 序列號碼：36 序列長度：3 1 序列型：核酸鏈數：1 局部解剖狀：直鏈狀序列種類：合成DNA (引物C22SF) 序列： AAAACAATAA AGGCAAGCAA ACCCAGTGAC C 31 序列號碼：37 序列長度：3 1 (請先閱讀背面之注意事項再填寫本頁) €衣· 訂 4 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 104 3 8 0 7 6 538049 A7 B7 五、發明説明（105) 序列型：核酸鐽數：1 局部解剖狀：直鏈狀序列種類：合成D N A (引物C 2 2 S R ) 序列： GGTCACTGGG TTTGCTTGCC TTTATTGTTT T 31 序列號碼：38 序列長度：3 1 序列型：核酸鏈數：1 局部解剖狀：直鏈狀序列種類：合成DHA(引物C23SF) 序列： TCAGTAAAAA TAAGCAGCTT ATAACTGGCC A 31 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) 序列號碼：39 序列長度：3 1 序列型：核酸鐽數：1 局部解剖狀：直鏈狀序列種類··合成D N A (引物C 2 3 S R ) 序列： TGGCCAGTTA TAAGCTGCTT ATTTTTACTG A 31 序列號碼：40 序列長度：22 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 105 38 0 76 538049 A7 B7 經濟部中央標準局員工消費合作社印製五、發明説明（1 06) 序列型：核酸鏈數：1 局部解剖狀：直鏈狀序列種類：合成DNA (引物IF14) 序列： TTGGGGTTTA TTGGAGGAGA TG 22 序列號碼：41 序列長度：36 序列型：核酸鏈數：1 局部解剖狀：直鐽狀序列種類：合成DN A (引物DCR1F) 序列： ACCACCCAGG AACCTTGCCC TGACCACTAC TACAC A 36 序列號碼：4 2 序列長度：36 序列型：核酸鏈數：1 局部解剖狀：直鏈狀序列種類：合成DNA(引物DCR1R) 序列： GTCAGGGCAA GGTTCCTGGG TGGTCCACTT AATGGA 36 序列號碼：43 序列長度：36 (請先閱讀背面之注意事項再填寫本頁) 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 106 38 0 7 6 538049 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明（1 07) 序列型：核酸鏈數：1 局部解剖狀：直鐽狀序列種類：合成DNA (引物DCR2F) 序列： ACCGTGTGCG CCGAATGCAA GGAAGGGCGC TACCTT 36 序列號碼：44 序列長度：36 序列型：核酸鏈數：1 局部解剖狀：直鏈狀序列種類：合成DNA (引物DCR2R) 序列： TTCCTTGCAT TCGGCGCAC A CGGTCTTCCA CTTTGC 36 序列號碼：45 序列長度：36 序列型：核酸鏈數：1 局部解剖狀：直鐽狀序列種類：合成DNA (引物DCR3F) 序列： AACCGCGTGT GCAGATGTCC AGATGGGTTC TTCTCA 36 序列號碼：46 序列長度：36 (請先閱讀背面之注意事項再填寫本頁)Arg Arg Arg Pro Lys Pro Gin ile Cys lie 115 120 125 Serial number: 1 6 Sequence length: 20 This paper size applies to the Chinese National Standard (CNS) A4 size (210X 297 mm) 97 3 8 0 7 6 538049 A7 B7 5 Explanation of the invention (98) Sequence type: Nucleic acid strand number: 1 Local anatomy: Linear sequence type: Synthetic DNA (primer T3) Sequence: A ATTAACCCT CACTAAAGGG 20 Sequence number: 1 7 Sequence length: 22 Sequence type: Nucleic acid Number: 1 Local anatomy: Linear sequence Type: Synthetic DNA (primer T7) Sequence: GTAATACGAC TCACTATAGG GC 22 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling this page) Sequence number : 1 8 Sequence length: 20 Sequence type: Nucleic acid strand number: 1 Local anatomy: Linear sequence type: Synthetic DN A (primer IF 1) Sequence: ACATCAAAAC AAAGACCAAG 20 Sequence number: 1 9 Sequence length: 20 Paper size Applicable to China National Standard (CNS) A4 specification (210 X 297 mm) 98 3 8 0 7 6 538049 A7 B7 V. Description of the invention (9 9) Sequence type: Nucleic acid strand number: 1 Local anatomy : Linear sequence type: Synthetic DNA (primer IF2) Sequence: TCTTGGTCTT TGTTTTGATG 20 Sequence number: 20 Sequence length: 20 Sequence type: Nucleic acid chain number: 1 Local anatomy: Linear sequence type ·· Synthetic DNA (primer IF 3) Sequence: TTATTCGCCA CAAACTGAGC 20 Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs (please read the notes on the back before filling this page) Sequence Number: 2 1 Sequence Length: 20 Sequence Type: Nucleic Acid Chain Number: 1 Partial Anatomy ： Straight-chain sequence type: Synthetic DN A (primer IF4) Sequence: TTGTGAAGCT GTGAAGGAAC 20 Sequence number: Sequence length: 20 This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) 99 3 8 0 7 6 538049 A7 B7 V. Description of the invention (1 00) Sequence type: Nucleic acid strand number: 1 Local anatomy: Mullion sequence type: Synthetic DNA (primer IF5) Sequence: GCTCAGTTTG TGGCGAATAA 20 Sequence number: 23 Sequence length: 20 Sequence type: Number of nucleic acid strands: 1 Local anatomy: linear sequence Type: synthetic DNA (primer IF6) Sequence: GTGGGAGCAG AAGACATTGA 20 Ministry of Economic Affairs Printed by the Consumer Bureau of Standards Bureau (please read the precautions on the back before filling out this page) Sequence Number: 24 Sequence Length: 20 Sequence Type: Nucleic Acid Chain Number: 1 Local Anatomy: Linear Sequence Type: Synthetic DNA (primer IF7) Serial: AATGAACAAC TTGCTGTGCT 20 Serial number: 25 Serial length: 20 This paper size applies to the Chinese National Standard (CNS) A4 specification (210X 297 mm) 100 3 8 0 7 6 538049 A7 B7 Employee Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs Printed 5. Description of the invention (101) Sequence type: Nucleic acid strand number: 1 Local anatomy: Linear sequence number: Synthetic DNA (primer IF8) Sequence: TGACAAATGT CCTCCTGGTA 20 Sequence number: 26 Sequence length: 20 Sequence type: Nucleic acid chain number: 1 Partial anatomy: Linear sequence Type: Synthetic DN A (primer IF9) Sequence: AGGTAGGTAC CAGGAGGACA 20 Sequence number: 27 Sequence length: 20 Sequence type: Nucleic acid chain number: 1 Partial anatomy: Linear Sequence type: synthetic DN A (primer IF 10) sequence: GAGCTGCCCT CCTGGATTTG 20 sequence number: 28 sequence length: 20 (please read the first Please fill in this page for the matters needing attention.) ···· ττ d This paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm) 101 3 8 0 7 6 538049 A7 B7 Printed by the Staff Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs V. Description of the invention (102) 1 1 Sequence-type nucleic acid 1 I Number: 1 1 1 I Local anatomy: linear 1 1 1 Sequence type * Synthetic DN Α (primer IF1 1) Read back 1 1 sequence * Note 1 CAAACTGTAT TTCGCTCTGG 20 1 I Matter 1 I Sequence number: 29% Sequence length ♦ 20 Fill in this page 1 Sequence type: Nucleic acid, 〆1 I 鐽 Number: 1 1 1 1 Partial anatomy: straight chain 1 1 Order Sequence type: Synthetic DNA (primer IF12) 1 sequence; 1 1 GTGTGAGGAG GCATTCTTCA 20 1 | sequence trace m code: 30 4 sequence length: 32 1 I sequence type: nuclear • ΤΓ / Λ acid 1 1 chain number: 1 1 1 Local anatomy: linear 1 1 Sequence type Synthetic DNA (primer C19SF) 1 1 Sequence: 1 I GAATCAACTC AAAAAAGTGG AATAGATGTT AC 32 1 I serial number ♦ · 31 1 1 I serial length * 3 2 1 1 This paper size applies to China National Standard (CNS) A4 size (210X 297 mm) 102 3 8 0 7 6 538049 A7 B7 Ministry of Economy Printed by the Consumer Standards Cooperative of the Central Bureau of Standards 5. Description of the invention (1 0 3) Sequence type: Nucleic acid strand number: 1 Local anatomy: Linear sequence Type: Synthetic DNA (primer C19SR) Sequence: GTAACATCTA TTCCACTTTT TTGAGTTGAT TC 32 Sequence number · 32 sequence length: 30 sequence type · number of nucleic acids: 1 local anatomy: linear sequence type: synthetic DN A (primer C20SF) sequence: ATAGATGTTA CCCTGAGTGA GGAGGCATTC 30 sequence number: 33 sequence length: 30 sequence type: Nucleic acid strand number: 1 Local anatomy: linear sequence type: synthetic DNA (primer C20SR) sequence: GAATGCCTCC TCACTCAGGG TAACATCTAT 30 sequence number: 34 sequence length: 3 1 (please read the precautions on the back before filling this page) Order __ · This paper size applies to China National Standard (CNS) A4 size (210X 297 mm) 103 38 0 7 6 538049 A7 B7 Economy Printed by the Consumer Standards Cooperative of the Ministry of Standards of the People's Republic of China. 5. Description of the invention (104) Sequence type: Nucleic acid strand number: 1 Local anatomy: Linear sequence type: Synthetic DNA (primer C 2 1 SF) Sequence: CAAGATATTG ACCTCAGTGA AAACAGCGTG C 31 Sequence number: 35 Sequence length: 3 1 Sequence type: Nucleic acid number: 1 Local anatomy: Orthogonal sequence Type: Synthetic DNA (primer C21SR) Sequence: GCACGCTGTT TTCACTGAGG TCAATATCTT G 31 Sequence number: 36 Sequence length: 3 1 Sequence Type: Nucleic acid strand number: 1 Local anatomy: Linear sequence Type: Synthetic DNA (primer C22SF) Sequence: AAAACAATAA AGGCAAGCAA ACCCAGTGAC C 31 Sequence number: 37 Sequence length: 3 1 (Please read the notes on the back before filling in this Page) € Clothes · Order 4 This paper size applies Chinese National Standard (CNS) A4 size (210X 297 mm) 104 3 8 0 7 6 538049 A7 B7 V. Description of the invention (105) Sequence type: Nucleic acid number: 1 Partial Anatomy: linear sequence type: synthetic DNA (primer C 2 2 SR) sequence: GGTCACTGGG TTTGCTTGCC TTTATTGTTT T 31 sequence number: 38 sequence length Degree: 3 1 Sequence type: Nucleic acid strand number: 1 Local anatomy: Linear sequence Type: Synthetic DHA (primer C23SF) Sequence: TCAGTAAAAA TAAGCAGCTT ATAACTGGCC A 31 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please read the back first) Please fill in this page again) Sequence number: 39 Sequence length: 3 1 Sequence type: Nucleic acid number: 1 Local anatomy: Linear sequence type · Synthetic DNA (primer C 2 3 SR) Sequence: TGGCCAGTTA TAAGCTGCTT ATTTTTACTG A 31 Serial number: 40 Serial length: 22 This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) 105 38 0 76 538049 A7 B7 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 06) Sequence type: Nucleic acid strand number: 1 Local anatomy: Linear sequence type: Synthetic DNA (primer IF14) Sequence: TTGGGGTTTA TTGGAGGAGA TG 22 Sequence number: 41 Sequence length: 36 Sequence type: Nucleic acid strand number: 1 Local anatomy State: Mullion sequence type: synthetic DNA (primer DCR1F) sequence: ACCACCCAGG AACCTTGCCC TGACCACTAC TACAC A 36 sequence number: 4 2 Sequence length: 36 Sequence type: Number of nucleic acid strands: 1 Local anatomy: Linear sequence type: Synthetic DNA (primer DCR1R) Sequence: GTCAGGGCAA GGTTCCTGGG TGGTCCACTT AATGGA 36 Sequence number: 43 Sequence length: 36 (Please read the back first Please note this page before filling in this page) This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) 106 38 0 7 6 538049 A7 B7 printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (1 07 ) Sequence type: Nucleic acid strand number: 1 Local anatomy: Mullion sequence type: Synthetic DNA (primer DCR2F) Sequence: ACCGTGTGCG CCGAATGCAA GGAAGGGCGC TACCTT 36 Sequence number: 44 Sequence length: 36 Sequence type: Nucleic acid strand number: 1 State: Linear sequence type: Synthetic DNA (primer DCR2R) Sequence: TTCCTTGCAT TCGGCGCAC A CGGTCTTCCA CTTTGC 36 sequence number: 45 sequence length: 36 sequence type: number of nucleic acid strands: 1 local anatomy: straight sequence type: synthetic DNA (Primer DCR3F) sequence: AACCGCGTGT GCAGATGTCC AGATGGGTTC TTCTCA 36 sequence number: 46 sequence length: 36 ( Notes on the back read and then fill this page)

、tT _d 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 107 3 8 0 7 6 538049 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明（1 08) 序列型：核酸鐽數：1 局部解剖狀：直鐽狀序列種類：合成D N A (引物D C R 3 R ) 序列： ATCTGGAC AT CTGCACACGC GGTTGTGGGT GCGATT 36 序列號碼：47 序列長度：36 序列型：核酸鏈數：1 局部解剖狀：直鏈狀序列種類：合成DNA (引物DCR4F) 序列： ACAGTTTGCA AATCCGGAAA CAGTGAATCA ACTCAA 36 序列號碼：48 序列長度：3 6 序列型：核酸鐽數：1 局部解剖狀：直鏈狀序列種類：合成D N A (引物D C R 4 R ) 序列： ACTGTTTCCG GATTTGCAAA CTGTATTTCG CTCTGG 36 序列號碼：49 序列長度：36 (請先閱讀背面之注意事項再填寫本頁) €衣- 、?! 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 108 3 8 0 7 6 538049 A7 B7 經濟部中央標準局員工消費合作社印製五、發明説明（1 0 9) 序列型：核酸鏈數：1 局部解剖狀：直鐽狀序列種類：合成DNA(引物DDD1F) 序列： AATGTGGA AT AGATATTGAC CTCTGTGAAA ACAGCG 36 序列號碼：50 序列長度：36 序列型：核酸鏈數：1 局部解剖狀：直鏈狀序列種類：合成DNA (引物DDD1R) 序列： AGAGGTCA AT ATCTATTCCA CATTTTTGAG TTGATT 36 序列號碼：5 1 序列長度：36 序列型：核酸鍵數：1 局部解剖狀：直鏈狀序列種類：合成DNA (引物DDD2F) 序列： AGATCATCCA AGACGCACTA AAGCACTCAA AGACGT 36 序列號碼：5 2 序列長度：36 (請先閱讀背面之注意事項再填寫本頁) €衣-、 TT _d This paper size is applicable to Chinese National Standard (CNS) A4 specification (210X 297 mm) 107 3 8 0 7 6 538049 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of invention (1 08) Serial type : Number of Nucleic Acids: 1 Partial Anatomy: Orthogonal Sequence Type: Synthetic DNA (primer DCR 3 R) Sequence: ATCTGGAC AT CTGCACACGC GGTTGTGGGT GCGATT 36 Sequence Number: 47 Sequence Length: 36 Sequence Type: Nucleic Acid Chain: 1 Partial Anatomy State: Linear sequence type: Synthetic DNA (primer DCR4F) Sequence: ACAGTTTGCA AATCCGGAAA CAGTGAATCA ACTCAA 36 Sequence number: 48 Sequence length: 3 6 Sequence type: Nucleic acid number: 1 Local anatomy: Linear sequence type: Synthetic DNA (Primer DCR 4 R) sequence: ACTGTTTCCG GATTTGCAAA CTGTATTTCG CTCTGG 36 sequence number: 49 sequence length: 36 (please read the precautions on the back before filling this page) €--?! This paper size applies Chinese National Standard (CNS) A4 specification (210X 297 mm) 108 3 8 0 7 6 538049 A7 B7 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs Ming (1 0 9) Sequence type: Nucleic acid strand number: 1 Local anatomy: Mullion sequence type: Synthetic DNA (primer DDD1F) Sequence: AATGTGGA AT AGATATTGAC CTCTGTGAAA ACAGCG 36 Sequence number: 50 Sequence length: 36 Sequence type: Nucleic acid Number of strands: 1 Partial anatomy: Linear sequence Type: Synthetic DNA (primer DDD1R) Sequence: AGAGGTCA AT ATCTATTCCA CATTTTTGAG TTGATT 36 Sequence number: 5 1 Sequence length: 36 Sequence type: Nucleic acid bond: 1 Type of chain sequence: synthetic DNA (primer DDD2F) sequence: AGATCATCCA AGACGCACTA AAGCACTCAA AGACGT 36 sequence number: 5 2 sequence length: 36 (please read the precautions on the back before filling this page)

、1T d 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 109 3 8 07 6 538049 A7 B7 五、發明説明（1 1 〇) 序列型：核酸鏈數：1 局部解剖狀：直鏈狀序列種類：合成DNA (引物DDD2R) 序列： GCTTTAGTGC GTCTTGGATG ATCTTCTTGA CTATAT 36 序列號碼：53 序列長度：29 序列型：核酸鏈數：1 局部解剖狀：直鏈狀序列種類：合成D N A (引物X h ο I F ) 序列： GGCTCGAGCG CCCAGCCGCC GCCTCCAAG 29 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) 序列號碼：5 4 序列長度：20 序列型：核酸鏈數：1 局部解剖狀：直鏈狀序列種類··合成D N A (引物I F 1 6 ) 序列： TTTG AGTGCT TTAGTGCGTG 20 序列號碼：55 序列長度：30 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 110 3 8 0 7 6 經濟部中央標準局員工消費合作社印製 538049 、 A7 B7 五、發明説明（1 1 1) 序列型：核酸鐽數：1 局部解剖狀：直鏈狀序列種類：合成DNA (引物CLF) 序列： TCAGTAAAAA TAAGCTAACT GGAAATGGCC 30 序列號碼：56 序列長度：30 序列型：核酸鏈數：1 局部解剖狀：直鏈狀序列種類：合成DN A (引物CLR) 序列： GGCCATTTCC AGTTAGCTTA TTTTTACTGA 30 序列號碼：57 序列長度：29 序列型：核酸鏈數：1 局部解剖狀：直鏈狀序列種類：合成DNA (引物CCR) 序列： CCGGATCCTC AGTGCTTTAG TGCGTGCAT 29 序列號碼：58 序列長度：29 (請先閱讀背面之注意事項再填寫本頁) 、言本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 111 3 8 0 7 6 經濟部中央標準局員工消費合作社印製 538049 A7 B7 五、發明説明（112) 序列型：核酸鏈數：1 局部解剖狀：直鏈狀序列種類：合成DNA (引物CCD2R) 序列： CCGGATCCTC ATTGGATGAT CTTCTTGAC 29 序列號碼：59 序列長度：2 9 序列型：核酸鏈數：1 局部解剖狀：直鏈狀序列種類：合成D N A (引物C C D 1 R ) 序列： CCGGATCCTC ATATTCCAC A TTTTTGAGT 29 序列號碼：60 序列長度：29 序列型：核酸鏈數：1 局部解剖狀：直鏈狀序列種類：合成DNA (引物CCR4R) 序列： CCGGATCCTC ATTTGCA A AC TGTATTTCG 29 序列號碼：6 1 序列長度：29 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 1 1 2 3 8 0 7 6 (請先閱讀背面之注意事項再填寫本頁)、 1T d This paper size applies Chinese National Standard (CNS) A4 specification (210X 297 mm) 109 3 8 07 6 538049 A7 B7 V. Description of the invention (1 1 〇) Sequence type: Number of nucleic acid chains: 1 Local anatomy: Linear sequence type: synthetic DNA (primer DDD2R) Sequence: GCTTTAGTGC GTCTTGGATG ATCTTCTTGA CTATAT 36 sequence number: 53 sequence length: 29 sequence type: number of nucleic acid strands: 1 local anatomy: linear sequence type: synthetic DNA (primer X h ο IF) Sequence: GGCTCGAGCG CCCAGCCGCC GCCTCCAAG 29 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling out this page) Sequence number: 5 4 Sequence length: 20 Sequence type: Number of nucleic acid strands: 1 Local anatomy: Type of linear sequence · Synthetic DNA (primer IF 1 6) Sequence: TTTG AGTGCT TTAGTGCGTG 20 Sequence number: 55 Sequence length: 30 This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) 110 3 8 0 7 6 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 538049, A7 B7 V. Description of the invention (1 1 1) Sequence type: Nucleic acid Number: 1 Local anatomy: Linear sequence Type: Synthetic DNA (primer CLF) Sequence: TCAGTAAAAA TAAGCTAACT GGAAATGGCC 30 Sequence number: 56 Sequence length: 30 Sequence type: Nucleic acid strand number: 1 Local anatomy: Linear sequence type : Synthetic DN A (primer CLR) sequence: GGCCATTTCC AGTTAGCTTA TTTTTACTGA 30 sequence number: 57 sequence length: 29 sequence type: number of nucleic acid strands: 1 local anatomy: linear sequence type: synthetic DNA (primer CCR) sequence: CCGGATCCTC AGTGCTTTAG TGCGTGCAT 29 serial number: 58 serial length: 29 (please read the notes on the back before filling this page), the paper size applies the Chinese National Standard (CNS) A4 specification (210X 297 mm) 111 3 8 0 7 6 Economy Printed by the Consumer Standards Cooperative of the Ministry of Standards of the People's Republic of China 538049 A7 B7 V. Description of the invention (112) Sequence type: Number of nucleic acid strands: 1 Local anatomy: Linear sequence Type: Synthetic DNA (primer CCD2R) Sequence: CCGGATCCTC ATTGGATGAT CTTCTTGAC 29 Number: 59 Sequence length: 2 9 Sequence type: Nucleic acid strand number: 1 Local anatomy: Linear sequence type Synthetic DNA (primer CCD 1 R) Sequence: CCGGATCCTC ATATTCCAC A TTTTTGAGT 29 sequence number: 60 sequence length: 29 sequence type: number of nucleic acid strands: 1 local anatomy: linear sequence type: synthetic DNA (primer CCR4R) sequence: CCGGATCCTC ATTTGCA A AC TGTATTTCG 29 Serial number: 6 1 Serial length: 29 This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) 1 1 2 3 8 0 7 6 (Please read the notes on the back before filling in this page)

、1T 4 538049 A7 B7 五、發明説明（113) 序列型：核酸鐽數：1 局部解剖狀：直鐽狀序列種類：合成DNA(引物CCR3R) 序列： CCGGATCCTC ATTCGCACAC GCGGTTGTG 29 序列號碼：6 2 序列長度：401 序列型··胺基酸鏈數：1 局部解剖狀：直鏈狀序列種類：蛋白質（0 C I F - C 1 9 5 ) 序列：1T 4 538049 A7 B7 V. Description of the invention (113) Sequence type: Nucleic acid number: 1 Local anatomy: Orthogonal sequence Type: Synthetic DNA (primer CCR3R) Sequence: CCGGATCCTC ATTCGCACAC GCGGTTGTG 29 Sequence number: 6 2 Sequence length : 401 sequence type · amino acid chain number: 1 local anatomy: linear sequence type: protein (0 CIF-C 1 9 5) sequence:

Met Asn Asa Leu Leu Cys Cys Ala Lea Val Phe Lea Asp [le Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Gla Thr Phe Pro Pro Lys Tyr Leu His -5 -1 1 . 5Met Asn Asa Leu Leu Cys Cys Ala Lea Val Phe Lea Asp [le Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Gla Thr Phe Pro Pro Lys Tyr Leu His -5 -1 1. 5

Tyr Asp G1 u Glu Thr Ser H is Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20Tyr Asp G1 u Glu Thr Ser H is Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20

Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu (請先閱讀背面之注意事項再填寫本頁) •t衣· 訂經濟部中央標準局員工消費合作社印製 55 60 65 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 113 3 8 0 7 6 538049 A7 B7 五、發明説明（114)Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu (Please read the notes on the back before filling out this page) • t-shirts · Order printed by the Central Consumers Bureau of the Ministry of Economic Affairs Consumer Cooperatives 55 60 65 This paper size applies China National Standard (CNS) A4 specification (210X 297 mm) 113 3 8 0 7 6 538049 A7 B7 V. Description of the invention (114)

Gla Tyr Vat Lys Gin Glu Cys Asa Arg Thr His Asa Arg Val Cys 70 75 80Gla Tyr Vat Lys Gin Glu Cys Asa Arg Thr His Asa Arg Val Cys 70 75 80

Glu Cys Lys Glu Gly Arg Tyr Leu Glu Ile Glu Phe Cys Leu Lys 85 90 95Glu Cys Lys Glu Gly Arg Tyr Leu Glu Ile Glu Phe Cys Leu Lys 85 90 95

His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Gly Thr 100 105 110His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Gly Thr 100 105 110

Pro Glu Arg i\sa Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 115 120 125Pro Glu Arg i \ sa Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 115 120 125

His Asp Asn lie Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Ser 160 165 170His Asp Asn lie Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Ser 160 165 170

Gly Me Asp Val Thr Lea Cys Glu Glu Ala Phe Phe Arg Phe Ala 175 180 185Gly Me Asp Val Thr Lea Cys Glu Glu Ala Phe Phe Arg Phe Ala 175 180 185

Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg lie 205 210 215 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁)Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg lie 205 210 215 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (Please read the notes on the back before filling out this page)

Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe Gla Leu Leu Lys * 220 225 230Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe Gla Leu Leu Lys * 220 225 230

Leu Trp Lys His Gin Asn Lys Asp Gin Asp lie Val Lys Lys Ile 235 240 245 lie Gin Asp lie Asp Lea Cys Glu Asn Ser Vai Gin Arg His lie 250 255 260Leu Trp Lys His Gin Asn Lys Asp Gin Asp lie Val Lys Lys Ile 235 240 245 lie Gin Asp lie Asp Lea Cys Glu Asn Ser Vai Gin Arg His lie 250 255 260

Gly His Ala Asn Leu Thr Phe Glu Gla Leu Arg Ser Leu Met Glu 265 270 275 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 114 3 8 0 7 6 538049 A7 B7 五、發明説明（1 15)Gly His Ala Asn Leu Thr Phe Glu Gla Leu Arg Ser Leu Met Glu 265 270 275 This paper size applies to Chinese National Standard (CNS) A4 specification (210X 297 mm) 114 3 8 0 7 6 538049 A7 B7 V. Description of the invention ( 1 15)

Ser Leu Pro Gly Lys Lys Val Gly Ala Gla Asp [le Glu Lys Thr 280 285 290 lie Lys Ala Cys Lys Pro Ser Asp Gin Ile Leu Lys Leu Leu Ser 295 300 305Ser Leu Pro Gly Lys Lys Val Gly Ala Gla Asp [le Glu Lys Thr 280 285 290 lie Lys Ala Cys Lys Pro Ser Asp Gin Ile Leu Lys Leu Leu Ser 295 300 305

Leu Trp Arg lie Lys Asn Gly Asp Gin Asp Thr Leu Lys Gly Leu 310 315 320 ilet llis Ala Leu Lys His Ser Lys Thr Tyr His Phe Pro Lys Thr 325 330 335Leu Trp Arg lie Lys Asn Gly Asp Gin Asp Thr Leu Lys Gly Leu 310 315 320 ilet llis Ala Leu Lys His Ser Lys Thr Tyr His Phe Pro Lys Thr 325 330 335

Val Thr Gin Ser Leu Lys Lys Thr [le Arg Phe Leu llis Ser Phe 340 345 350Val Thr Gin Ser Leu Lys Lys Thr [le Arg Phe Leu llis Ser Phe 340 345 350

Thr ilet Tyr Lys Leu Tyr Gin Lys Leu Phe Leu Glu Met lie Gly 355 360 365Thr ilet Tyr Lys Leu Tyr Gin Lys Leu Phe Leu Glu Met lie Gly 355 360 365

Asn Gin Val G1n Ser Va 1 Lys I le Ser Cys Leu 370 375 380 序列號碼：6 3 序列長度：4 0 1 序列型：胺基酸鏈數：1 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) 局部解剖狀：直鐽狀序列種類：蛋白質（0 C I F - C 2 0 S ) 序列：Asn Gin Val G1n Ser Va 1 Lys I le Ser Cys Leu 370 375 380 Sequence number: 6 3 Sequence length: 4 0 1 Sequence type: Amino acid chain number: 1 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs Read the notes on the reverse side and fill out this page) Partial anatomy: Mullion-like sequence Type: Protein (0 CIF-C 2 0 S) Sequence:

Met Asa Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp [le Ser ， -15 [le Lys Trp Thr Thr Gla Glu Thr Phe Pro Pro Lys Tyr Lea His -5 -1 1 5 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 115 3 8 0 7 6 538049 A7 B7 五、發明説明（116)Met Asa Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp [le Ser, -15 [le Lys Trp Thr Thr Gla Glu Thr Phe Pro Pro Lys Tyr Lea His -5 -1 1 5 This paper size applies to Chinese national standards (CNS ) A4 specification (210X297 mm) 115 3 8 0 7 6 538049 A7 B7 V. Description of the invention (116)

Tyr Asp Gla Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20Tyr Asp Gla Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20

Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arij Val Cys TO 75 80Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arij Val Cys TO 75 80

Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Leu Lys 85 90 95Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Leu Lys 85 90 95

Cys Ser Val Phe Gly Lea Lea Lea Tnr Gin Lys Gly Asn Ala Thr 145 150 155 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁)Cys Ser Val Phe Gly Lea Lea Lea Tnr Gin Lys Gly Asn Ala Thr 145 150 155 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (Please read the notes on the back before filling out this page)

His Asp Asn lie Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Cys ' 160 165 170His Asp Asn lie Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Cys' 160 165 170

Gly lie Asp Val Thr Leu Ser Glu Glu Ala Phe Phe Arg Phe Ala 175 180 185Gly lie Asp Val Thr Leu Ser Glu Glu Ala Phe Phe Arg Phe Ala 175 180 185

Asn Leu Pro Gly Thr Lys Vai Asn Ala Gla Ser Val Glu Arg lie 205 210 215 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 38076 538〇49 A7 經濟部中央標準局員工消費合作社印製 B7 五、發明説明 (11 7) 1 1 Lys Arg Gin His Ser Ser Gin G1 ii Gin Thr Phe Gin Leu Leu Lys 1 1 220 225 230 1 1 Lea Trp Lys His Gin Asn Lys Asp Gin Asp He Val Lys Lys lie 1 I 235 240 245 請先 1 1 I ie Gin Asp lie Asp Leu Cys Glu Asn Ser Val Gin Arg His lie 閱讀 1 背 1 250 255 260 之 1 G l y His Ala Asn Leu Thr Phe Glu Gin Leu Arg Ser Leu Me t Glu 注意 1 I 事 1 265 270 275 項再 1 t Ser Leu Pro G ly Lys Lys Val G ly Ala Glu Asp He Glu Lys Thr 填寫本 280 285 290 頁 1 I Ue Lys Ala Cys Lys Pro Ser Asp Gin He Lea Lys Leu Leu Ser 1 1 295 300 305 1 I Leu Trp Arg I ie Lys Asn G ly Asp Gin Asp Thr Leu Lys Gly Leu 1 1 310 315 320 訂 I Met His Ala Leu Lys His Ser Lys Thr Tyr His Phe Pro Lys Thr 1 1 325 330 335 1 | Val Thr Gin Ser Leu Lys Lys Thr I ie Arg Phe Leu H is Ser Phe 340 345 350 ά Thr Me t Ty r Lys Leu Tyr Gin Lys Lea Phe Leu Glu Me t lie Gly 1 | 355 360 365 1 1 • Asn Gin Val Gin Ser Val Lys I le Ser Cys Leu 1 I 370 375 380 1 1 I 序列號碼： 64 1 1 1 序列長度： 40 丨1 1 1 序列型 :胺基酸 1 I 鐽數： 1 1 I 局部解剖狀：直丨键狀 1 1 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 117 3 8 0 7 6 538049 A7 經濟部中央標準局員工消費合作社印製 B7 五、發明説明（1 1 8) 1 1 序列種類：蛋白質（OC IF-C21S) 1 I 序列： 1 1 I Met Asn Asn Leu Leu Cys Cys Ala Lea Val Phe Leu Asp [le Ser /-—V 請 1 1 I ^20 -15 -10 先閱讀背面意事 1 1 I le Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His 1 -5 -1 1 5 1 1 Ty r Asp Glu G l u Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 1 項 | 10 15 20 再填 % Pro G ly Thr Ty r Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 寫本頁 1 25 30 35 1 Vai Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp W[z 1 I 40 45 50 1 1 Thr Ser Asp G l u Cys Lea Tyr Cys Ser Pro Val Cys Lys Glu Leu 1 訂 1 55 60 65 Gla Ty r Val Lys Gla Glu Cys Asn Arg Thr His Asn Arg Val Cys 1 I 70 75 80 1 1 I G l u Cys Lys Glu G l y Arg Tyr Leu Glu I le Glu Phe Cys Leu Lys 1 ά I 85 90 95 His Arg Ser Cys Pro Pro Gly Phe Gly Val Vai Gin Ala Gly Thr 1 1 100 105 110 1 I Pro Giu Arg Asn Thr Vai Cys Lys Arg Cys Pro Asp Gly Phe Phe 1 1 115 120 125 1 I Ser Asn G l u Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 1 1 130 135 140 1 I Cys Ser Val Phe Gly Lea Leu Leu Thr Gin Lys Gly Asn Ala Thr 1 1 145 150 155 I | His Asp Asa [le Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Cys 1 I 160 165 170 1 1 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 118 3 80 7 6 538049 A7 B7 五、發明説明（11 9)Asn Leu Pro Gly Thr Lys Vai Asn Ala Gla Ser Val Glu Arg lie 205 210 215 This paper size applies to China National Standard (CNS) A4 (210X297 mm) 38076 538〇49 A7 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs B7 V. Description of the invention (11 7) 1 1 Lys Arg Gin His Ser Ser Gin G1 ii Gin Thr Phe Gin Leu Leu Lys 1 1 220 225 230 1 1 Lea Trp Lys His Gin Asn Lys Asp Gin Asp He Val Lys Lys lie 1 I 235 240 245 Please 1 1 I I Gin Asp lie Asp Leu Cys Glu Asn Ser Val Gin Arg His lie Read 1 Back 1 250 255 260 1 G ly His Ala Asn Leu Thr Phe Glu Gin Leu Arg Ser Leu Me t Glu Note 1 I matter 1 265 270 275 items and 1 t Ser Leu Pro G ly Lys Lys Val G ly Ala Glu Asp He Glu Lys Thr fill out this 280 285 290 page 1 I Ue Lys Ala Cys Lys Pro Ser Asp Gin He Lea Lys Leu Leu Ser 1 1 295 300 305 1 I Leu Trp Arg I ie Lys Asn G ly Asp Gin Asp Thr Leu L ys Gly Leu 1 1 310 315 320 Order I Met His Ala Leu Lys His Ser Lys Thr Tyr His Phe Pro Lys Thr 1 1 325 330 335 1 | Val Thr Gin Ser Leu Lys Lys Thr I ie Arg Phe Leu H is Ser Phe 340 345 350 ά Thr Me t Ty r Lys Leu Tyr Gin Lys Lea Phe Leu Glu Me t lie Gly 1 | 355 360 365 1 1 • Asn Gin Val Gin Ser Val Lys I le Ser Cys Leu 1 I 370 375 380 1 1 I sequence Number: 64 1 1 1 Sequence length: 40 丨 1 1 1 Sequence type: Amino acid 1 I Number of loops: 1 1 I Local anatomy: Straight 丨 bond 1 1 This paper size applies to China National Standard (CNS) A4 specifications (210X 297 mm) 117 3 8 0 7 6 538049 A7 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs B7 V. Description of the invention (1 1 8) 1 1 Sequence type: Protein (OC IF-C21S) 1 I Sequence: 1 1 I Met Asn Asn Leu Leu Cys Cys Ala Lea Val Phe Leu Asp [le Se r / -— V Please read 1 1 I ^ 20 -15 -10 Read the meaning on the back 1 1 I le Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His 1 -5 -1 1 5 1 1 Ty r Asp Glu G lu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 1 item | 10 15 20 Refill% Pro G ly Thr Ty r Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr Write this page 1 25 30 35 1 Vai Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp W [z 1 I 40 45 50 1 1 Thr Ser Asp G lu Cys Lea Tyr Cys Ser Pro Val Cys Lys Glu Leu 1 Order 1 55 60 65 Gla Ty r Val Lys Gla Glu Cys Asn Arg Thr His Asn Arg Val Cys 1 I 70 75 80 1 1 IG lu Cys Lys Glu G ly Arg Tyr Leu Glu I le Glu Phe Cys Leu Lys 1 ά I 85 90 95 His Arg Ser Cys Pro Pro Gly Phe Gly Val Vai Gin Ala Gly Thr 1 1 100 105 110 1 I Pro Giu Arg Asn Thr Vai Cys Lys Arg Cys Pro Asp Gly Phe Phe 1 1 115 120 125 1 I Ser Asn G lu Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 1 1 130 135 140 1 I Cys Ser Val Phe Gly Lea Leu Leu Thr Gin Lys Gly Asn Ala Thr 1 1 145 150 155 I | His Asp Asa [le Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Cys 1 I 160 165 170 1 1 This paper size applies to Chinese National Standard (CNS) A4 specification (210X 297 mm) 118 3 80 7 6 538049 A7 B7 V. Description of the invention (11 9)

Gly lie Asp Val Thr Leu Cys Glu Glu Ala Phe Phe Arg Phe Ala 175 180 185Gly lie Asp Val Thr Leu Cys Glu Glu Ala Phe Phe Arg Phe Ala 175 180 185

Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Set Val Leu Val Asp 190 195 200Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Set Val Leu Val Asp 190 195 200

Asa Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Vai Glu Arg lie 205 210 215Asa Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Vai Glu Arg lie 205 210 215

Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe Gin Lea Lea Lys 220 225 230Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe Gin Lea Lea Lys 220 225 230

Leu Trp Lys His Gla Asn Lys Asp Gin Asp fie Val Lys Lys lie 235 240 245 lie Gin Asp lie Asp Leu Ser Gla Asn Ser Val Gla Arg His lie 250 255 260Leu Trp Lys His Gla Asn Lys Asp Gin Asp fie Val Lys Lys lie 235 240 245 lie Gin Asp lie Asp Leu Ser Gla Asn Ser Val Gla Arg His lie 250 255 260

Gly His Ala Asn Lea Thr Phe Glu Gin Leu Arg Ser Leu Met Glu 265 270 275Gly His Ala Asn Lea Thr Phe Glu Gin Leu Arg Ser Leu Met Glu 265 270 275

Ser Leu Pro Gly Lys Lys Val Gly Ala Glu Asp lie Glu Lys Thr 280 285 290 [le Lys A la Cys Lys Pro Ser Asp Glη Ile Leu Lys Leu Leu Ser 295 300 305Ser Leu Pro Gly Lys Lys Val Gly Ala Glu Asp lie Glu Lys Thr 280 285 290 [le Lys A la Cys Lys Pro Ser Asp Glη Ile Leu Lys Leu Leu Ser 295 300 305

Leu Trp Arg Ile Lys Asn Gly Asp Gin Asp Thr Leu Lys Gly Leu 310 315 320 經濟部中央標準局員工消費合作社印製 (請先閲讀背面之注意事項再填寫本頁) ilet His Ala Leu Lys His Ser Lys Thr Tyr His Phe Pro Lys Thr 325 330 335Leu Trp Arg Ile Lys Asn Gly Asp Gin Asp Thr Leu Lys Gly Leu 310 315 320 Printed by the Staff Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (Please read the notes on the back before filling this page) ilet His Ala Leu Lys His Ser Lys Thr Tyr His Phe Pro Lys Thr 325 330 335

Val Thr Gin Ser Leu Lys Lys Thr lie Arg Phe Leu His Ser Phe 340 345 350Val Thr Gin Ser Leu Lys Lys Thr lie Arg Phe Leu His Ser Phe 340 345 350

Thr ilet Tyr Lys Leu Tyr Gin Lys Leu Phe Lea Glu Met [le Gly 355 360 365Thr ilet Tyr Lys Leu Tyr Gin Lys Leu Phe Lea Glu Met [le Gly 355 360 365

Asn Gin Val Gla Ser Val Lys Ile Ser Cys Leu 37j 375 380 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 119 3 8 0 7 6 ^38049Asn Gin Val Gla Ser Val Lys Ile Ser Cys Leu 37j 375 380 This paper size applies to China National Standard (CNS) A4 size (210X 297 mm) 119 3 8 0 7 6 ^ 38049

五、發明説明（〗2〇) 寧列號碼：65 $列長度：401 序列變：胺基酸 _數：！ _ ^解剖狀：直鏈狀 $列種類：蛋白質（0CIF-C22S) 序列： lV，et Asn Aan Lea Leu Cys Cya Ala Leu Va[ Pho Lea Asp [le Ser '20 -15 .10V. Description of the invention (〗 2〇) Ning column number: 65 $ column length: 401 sequence change: amino acid _ number :! _ ^ Anatomy: Linear $ Type of column: Protein (0CIF-C22S) Sequence: lV, et Asn Aan Lea Leu Cys Cya Ala Leu Va [Pho Lea Asp [le Ser '20 -15 .10

Lys Trp Thr Thr Gin Gla Thr Phe Pro Pro Lys Tyr Leu His -1 1 5 hr Asp Glu G1 u Thr Ser His Gin Leu Lea Cys Asp Lys Cys Pro 15 20Lys Trp Thr Thr Gin Gla Thr Phe Pro Pro Lys Tyr Leu His -1 1 5 hr Asp Glu G1 u Thr Ser His Gin Leu Lea Cys Asp Lys Cys Pro 15 20

Gly Thr Tyr Lea Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35Gly Thr Tyr Lea Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35

Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50

Thr Ser Asp Gla Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 經濟部中央標準局員工消費合作社印製 (請先閲讀背面之注意事項再填寫本頁)Thr Ser Asp Gla Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Printed by the Staff Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (Please read the notes on the back before filling out this page)

Glu Cys Lys Gla Gly Arg Tyr Leu Glu tie Gla Phe Cys Leu Lys 85 90 95Glu Cys Lys Gla Gly Arg Tyr Leu Glu tie Gla Phe Cys Leu Lys 85 90 95

His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gia Ala Gly Thr 100 105 110His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gia Ala Gly Thr 100 105 110

Pro Glu Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 1：3 120 125 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 120 3 8 0 76 538049 經濟部中央標準局員工消費合作社印製 A7 B7五、發明説明（1 2 1) Ser Asn G.1 a Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 130 135 140 Cys Ser Val Phe Gly Leu Leu Leu Thr Gin Lys Gly Asn Ala Thr 145 150 155 His Asp Asn I le Cys Ser Gly Asn Ser G1u Ser Thr Gin Lys Cys 160 165 170 Gly Me Asp Val Thr Leu Cys Gla Glu Ala Phe Phe Arg Phe Ala 175 ISO 185 Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val Lea Val Asp 190 195 200 Asn Lea Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg (le 205 210 215 Lys Arg Gin \\ is Ser Ser G1 n Glu Gin Thr Phe G i n Leu Leu Lys 220 225 230 Leu Trp Lys His Gin Asn Lys Asp Gln Asp Ile Val Lys Lys He 235 240 245 lie Gin Asp lie Asp Leu Cys Glu Asn Ser Val Gin Arg H is I Le 250 255 260 Gly His Ala Asn Leu Thr Phe Glu Gin Leu Arg Ser Lea Met Glu 265 270 275 Ser Leu Pro Gly Lys Lys Va1 G ίy A1 a Giu Asp [1e Glu Lys Thr 280 285 290 [le Lys Ala Ser Lys Pro Ser Asp Gln [le Leu Lys Leu Leu Ser 295 300 305 Leu Trp Arg Iie Lys Asn Gly Asp Gin Asp Thr Leu Lys Gly Leu 310 315 320 Met His Ala Leu Lys His Ser Lys Thr Tyr His Phe Pro Lys Thr 325 330 335 (請先閱讀背面之注意事項再填寫本頁) 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 121 38 0 76 538049 A7 B7 五、發明説明（l22)Pro Glu Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 1: 3 120 125 This paper size applies to China National Standard (CNS) A4 size (210X297 mm) 120 3 8 0 76 538049 Employees of the Central Bureau of Standards, Ministry of Economic Affairs Cooperative printed A7 B7 V. Description of the invention (1 2 1) Ser Asn G.1 a Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 130 135 140 Cys Ser Val Phe Gly Leu Leu Leu Thr Gin Lys Gly Asn Ala Thr 145 150 155 His Asp Asn I le Cys Ser Gly Asn Ser G1u Ser Thr Gin Lys Cys 160 165 170 Gly Me Asp Val Thr Leu Cys Gla Glu Ala Phe Phe Arg Phe Ala 175 ISO 185 Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val Lea Val Asp 190 195 200 Asn Lea Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg (le 205 210 215 Lys Arg Gin \\ is Ser Ser G1 n Glu Gin Thr Phe G in Leu Leu Lys 220 225 230 Leu Trp Lys His Gin Asn Lys Asp Gln Asp Ile Val Lys Lys He 235 240 245 lie Gin Asp lie Asp Leu Cys Glu Asn Ser Val Gin Arg H is I Le 250 255 260 Gly His Ala Asn Leu Thr Phe Glu Gin Leu Arg Ser Lea Met Glu 265 270 275 Ser Leu Pro Gly L ys Lys Va1 G ίy A1 a Giu Asp [1e Glu Lys Thr 280 285 290 [le Lys Ala Ser Lys Pro Ser Asp Gln [le Leu Lys Leu Leu Ser 295 300 305 Leu Trp Arg Iie Lys Asn Gly Asp Gin Asp Thr Leu Lys Gly Leu 310 315 320 Met His Ala Leu Lys His Ser Lys Thr Tyr His Phe Pro Lys Thr 325 330 335 (Please read the precautions on the back before filling this page) This paper size applies to Chinese National Standard (CNS) A4 specification (210X297 Mm) 121 38 0 76 538049 A7 B7 V. Description of the invention (l22)

Thr Met Tyr Lys Leu Tyr Gin Lys Leu Phe Leu Glu Met lie Gty 355 360 365Thr Met Tyr Lys Leu Tyr Gin Lys Leu Phe Leu Glu Met lie Gty 355 360 365

Asn Gin Vai Gin Ser Val Lys lie Ser Cys Leu 370 375 380 序列號碼：66 序列長度·· 401 序列型：胺基酸鏈數：1 局部解剖狀：直鏈狀序列種類：蛋白質（0CIF-C23S) 序列：Asn Gin Vai Gin Ser Val Lyslie Ser Cys Leu 370 375 380 sequence number: 66 sequence length · 401 sequence type: amino acid chain number: 1 local anatomy: linear sequence type: protein (0CIF-C23S) sequence :

Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Lea Asp lie Ser -20 -lo -10Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Lea Asp lie Ser -20 -lo -10

He Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Lea His -5 -11 5 考經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁)He Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Lea His -5 -11 5 Exam Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (Please read the precautions on the back before filling this page)

Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Gta Lea 55 60 65 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 122 3 8 0 7 6 538049 A7 B7 五、發明説明（123)Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Gta Lea 55 60 65 This paper size applies to China National Standard (CNS) A4 specification (210X 297 mm) 122 3 8 0 7 6 538049 A7 B7 V. Description of the invention ( 123)

Gin Tyr Val Lys Gin Gla Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80Gin Tyr Val Lys Gin Gla Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80

Gla Cys Lys Glu Gly Arg Tyr Lea Glu lie Gla Phe Cys Lea Lys (請先閱讀背面之注意事項再填寫本頁) 85 90 95Gla Cys Lys Glu Gly Arg Tyr Lea Glu lie Gla Phe Cys Lea Lys (Please read the notes on the back before filling this page) 85 90 95

Ser Asn Glu Thr Ser Ser Lys A la Pro Cys rtrg Lys His Thr Asn 130 135 140Ser Asn Glu Thr Ser Ser Lys A la Pro Cys rtrg Lys His Thr Asn 130 135 140

Cys Ser Val Phe Gly Lea Leu Leu Thr Gin Lys Gly Asn Ala Thr 145 150 155Cys Ser Val Phe Gly Lea Leu Leu Thr Gin Lys Gly Asn Ala Thr 145 150 155

His Asp Asn [le Cys Ser Gly Asn Ser Glu Ser Thr Gln Lys Cys 160 165 170His Asp Asn [le Cys Ser Gly Asn Ser Glu Ser Thr Gln Lys Cys 160 165 170

Gly lie Asp Val Thr Leu Cys Gla Glu Ala Phe Phe Arg Phe Ala 175 180 185Gly lie Asp Val Thr Leu Cys Gla Glu Ala Phe Phe Arg Phe Ala 175 180 185

Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg lie 205 210 215 經濟部中央標準局員工消費合作社印製.Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg lie 205 210 215 Printed by the Staff Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs.

Leu Trp Lys His Gin Asn Lys Asp Gin Asp [le Val Lys Lys [ 1 e 235 240 245 [le Gin Asp lie Asp Lea Cys Glu Asa Ser Val Gin Arg His lie 250 255 260Leu Trp Lys His Gin Asn Lys Asp Gin Asp [le Val Lys Lys [1 e 235 240 245 [le Gin Asp lie Asp Lea Cys Glu Asa Ser Val Gin Arg His lie 250 255 260

Gly His Ala Asn Leu Thr Phe Glu Gin Leu Arg Ser Leu Met Glu 265 270 275 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 123 38 0 7 6 538049 A7 B7 五、發明説明（1 24)Gly His Ala Asn Leu Thr Phe Glu Gin Leu Arg Ser Leu Met Glu 265 270 275 This paper size applies to Chinese National Standard (CNS) A4 size (210X 297 mm) 123 38 0 7 6 538049 A7 B7 V. Description of the invention (1 twenty four)

Ser Leu Pro Gly Lys Lys Val Gly Ala Glu Asp lie Glu Lys Thr 280 285 290 lie Lys Ala Cys Lys Pro Ser Asp Gin lie Leu Lys Leu Lea Ser 295 300 305Ser Leu Pro Gly Lys Lys Val Gly Ala Glu Asp lie Glu Lys Thr 280 285 290 lie Lys Ala Cys Lys Pro Ser Asp Gin lie Leu Lys Leu Lea Ser 295 300 305

Leu Trp Arg lie Lys Asn Gly Asp Gin Asp Thr Leu Lys Gly Leu 310 31.5 320Leu Trp Arg lie Lys Asn Gly Asp Gin Asp Thr Leu Lys Gly Leu 310 31.5 320

Met His Ala Leu Lys His Ser Lys Thr Tyr His Phe Pro Lys Thr 325 330 335Met His Ala Leu Lys His Ser Lys Thr Tyr His Phe Pro Lys Thr 325 330 335

Thr tlet Tyr Lys Leu Tyr Gin Lys Lea Phe Leu Glu Met lie Gly 355 360 365Thr tlet Tyr Lys Leu Tyr Gin Lys Lea Phe Leu Glu Met lie Gly 355 360 365

Asa Gin Val Gin Ser Val Lys lie Ser Ser Leu 370 375 380 序列號碼：67 序列長度：360 序列型：胺基酸鏈數：1 局部解剖狀：直鏈狀序列種類：蛋白質（0CIF-DCR1) 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) 序列：Asa Gin Val Gin Ser Val Lyslie Ser Ser Leu 370 375 380 Sequence number: 67 Sequence length: 360 Sequence type: Amino acid chain number: 1 Local anatomy: Linear sequence type: Protein (0CIF-DCR1) Ministry of Economy Printed by the Consumer Standards Cooperative of the Central Bureau of Standards (Please read the notes on the back before filling this page)

Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp_[le Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Gla Pro Cys Pro Asp Hls Tyr Tyr Thr -5 -i i 5Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp_ [le Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Gla Pro Cys Pro Asp Hls Tyr Tyr Thr -5 -i i 5

Asp Ser Trp His Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val i〇 15 20 本紙張尺度適用中國國家標準（CNS )八4規格（210X297公釐） 124 3 8 0 7 6 538049 A7 -^___ B7 五、發明説明（！25)Asp Ser Trp His Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val i〇15 20 This paper size applies to the Chinese National Standard (CNS) 8 4 specifications (210X297 mm) 124 3 8 0 7 6 538049 A7-^ ___ B7 5 Description of the invention (! 25)

Lys Glu Leu Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His 25 30 35Lys Glu Leu Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His 25 30 35

Asn Arg Val Cys Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu (請先閱讀背面之注意事項再填寫本頁) 40 45 50Asn Arg Val Cys Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu (Please read the notes on the back before filling this page) 40 45 50

Phe Cys Leu Lys His Arg Ser Cys Pro Pro Gly Phe Gly Val Val 55 60 65Phe Cys Leu Lys His Arg Ser Cys Pro Pro Gly Phe Gly Val Val 55 60 65

Gin Ala Gly Thr Pro Gla Arg Asn Thr Val Cys Lys Arg Cys Pro 70 75 80Gin Ala Gly Thr Pro Gla Arg Asn Thr Val Cys Lys Arg Cys Pro 70 75 80

Asp Gly Phe Phe Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys Arg 85 90 95Asp Gly Phe Phe Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys Arg 85 90 95

Lys His Thr Asn Cys Ser Val Phe Gly Leu Leu Lea Thr Gin Lys i〇〇 105 110Lys His Thr Asn Cys Ser Val Phe Gly Leu Leu Lea Thr Gin Lys i〇〇 105 110

Gly Asn Ala Thr (iis Asp Asn lie Cys Ser Gly Asn Ser Gla Ser 115 120 125Gly Asn Ala Thr (iis Asp Asn lie Cys Ser Gly Asn Ser Gla Ser 115 120 125

Thr Gin Lys Cys Gly lie Asp Vai Thr Leu Cys Glu Glu Ala Phe 130 135 140Thr Gin Lys Cys Gly lie Asp Vai Thr Leu Cys Glu Glu Ala Phe 130 135 140

Phe Arg Phe Ala Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser 145 150 155Phe Arg Phe Ala Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser 145 150 155

Val Leu Val Asp Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser 160 165 170 經濟部中央標準局員工消費合作社印製Val Leu Val Asp Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser 160 165 170 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs

Val Gla Arg lie Lys Arg Gin His Ser Ser Gin Gla Gin Thr Phe 175 180 135Val Gla Arg lie Lys Arg Gin His Ser Ser Gin Gla Gin Thr Phe 175 180 135

Gin Leu Lea Lys Leu Trp Lys His Gin Asn Lys Asp Gin Asp I le 190 195 200Gin Leu Lea Lys Leu Trp Lys His Gin Asn Lys Asp Gin Asp I le 190 195 200

Val Ly3 Lys [le [le Gin Agp lie Asp Leu Cys G ί u Asn Ser Va l 205 210 215Val Ly3 Lys [le [le Gin Agp lie Asp Leu Cys G ί u Asn Ser Va l 205 210 215

Gin Arg His [le Gly His Ala Asn Leu Thr Phe Glu Gin Leu Arg 220 225 230 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 125 3 8 0 7 6 538049 A7 ___ B7____一 _____ 五、發明説明（126)Gin Arg His [le Gly His Ala Asn Leu Thr Phe Glu Gin Leu Arg 220 225 230 This paper size applies to Chinese National Standard (CNS) A4 size (210X297 mm) 125 3 8 0 7 6 538049 A7 ___ B7____ 一 _____ V. Invention Description (126)

Ser Leu Met Glu Ser Leu Pro Gly Lys Lys Val Gly Ala Glu Asp 235 240 245Ser Leu Met Glu Ser Leu Pro Gly Lys Lys Val Gly Ala Glu Asp 235 240 245

He Giu Lys Thr lie Lys Ala Cys Lys Pro Ser Asp Gin lie Leu (請先閲讀背面之注意事項再填寫本頁) 250 255 260He Giu Lys Thr lie Lys Ala Cys Lys Pro Ser Asp Gin lie Leu (Please read the notes on the back before filling this page) 250 255 260

Lys Leu Leu Ser Leu Trp Arg lie Lys Asn Gly Asp Gin Asp Thr 265 270 275Lys Leu Leu Ser Leu Trp Arg lie Lys Asn Gly Asp Gin Asp Thr 265 270 275

Leu Lys Gly Leu Met His Ala Leu Lys His Ser Lys Thr Tyr His 280 285 290Leu Lys Gly Leu Met His Ala Leu Lys His Ser Lys Thr Tyr His 280 285 290

Phe Pro Lys Thr Val Thr Gin Ser Leu Lys Lys Thr lie Arg Phe 295 300 305Phe Pro Lys Thr Val Thr Gin Ser Leu Lys Lys Thr lie Arg Phe 295 300 305

Lea His Ser Phe Thr Met Tyr Lys Leu Tyr Gin Lys Leu Phe Leu 310 315 320Lea His Ser Phe Thr Met Tyr Lys Leu Tyr Gin Lys Leu Phe Leu 310 315 320

Glu Met lie Gly Asn Gla Vai Gin Ser Val Lys He Ser Cys Leu 325 330 335 序列號碼：6 8 序列長度：359 序列型··胺基酸鏈數：1 經濟部中央標準局員工消費合作社印製局部解剖狀：直鏈狀序列種類：蛋白質（〇 C I F _ D C R 2 ) 序列：Glu Met lie Gly Asn Gla Vai Gin Ser Val Lys He Ser Cys Leu 325 330 335 Sequence number: 6 8 Sequence length: 359 Sequence type · Amino acid chain number: 1 Printed local anatomy by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs Shape: linear sequence type: protein (〇CIF _ DCR 2) sequence:

Me t Asn Asn Lea Leu Cys Cys A la Lea Val Phe Leu Asp [le Ser -20 -15 -10 [le Lys Trp Thr Thr Gin Gla Thr Phe Pro Pro Lys Tyr Leu His -i 1 5Me t Asn Asn Lea Leu Cys Cys A la Lea Val Phe Leu Asp [le Ser -20 -15 -10 [le Lys Trp Thr Thr Gin Gla Thr Phe Pro Pro Lys Tyr Leu His -i 1 5

Tyr Asp Gla G1 a Thr Ser His GIn Lea Lea Cys Asp Lys Cys Pro 10 15 20 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 126 3 8 0 7 6 538049 A7 B7 經濟部中央標準局員工消費合作社印製五、發明説明（1 27) 1 I Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 1 1 25 30 35 1 I Vai Cys Ala G1 u Cys Lys G l u Gly Arg Tyr Leu Glu Me Glu Phe 1 1 40 45 50 /^V 請 1 8 1 Cys Lea Lys His Arg Ser Cys Pro Pro Gly Phe Gly Vai Val Gin 閱讀 1 I 55 60 65 背 1 I 之 1 Ala Gly Thr Pro G1 u Arg Asn Thr Vai Cys Lys Arg Cys Pro Asp 注意 1 1 TO 75 80 事項 1 I G ly Phe Phe Ser Asn G I u Thr Ser Ser Lys Ala Pro Cys Arg Lys 再填寫 t 1 85 90 95 本頁 His Thr Asn Cys Ser Val Phe G l v Leu Leu Lea Thr Gin Lys Gly 1 I 100 105 110 1 1 I Asn Ala Thr His Asp Asn I le Cys Ser Gly Asn Ser Gia Ser Thr 1 1 115 120 125 訂 I Gin Lys Cys G 1 y [le Asp Val Thr Leu Cys G l u G l u Ala Phe Phe 1 1 130 135 140 1 I Arg Phe Ala Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val 1 1 145 150 155 4 Leu Val Asp Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val 1 I 160 165 170 1 1 G1 u Arg lie Lys Arg Gin His Ser Ser Gin Gla G 1 n Thr Phe Gin 1 I 175 180 185 1 1 Leu Leu Lys Lea Trp Lys His Gin Asn Lys Asp Gin Asp [le Val 1 I 190 195 200 1 1 Lys Lys He I le Gin Asp (le Asp Leu Cys G l a Asn Ser Val Gin 1 I 205 210 215 1 1 Arg His I le Gly His Ala Asn Leu Thr Phe G l a Gin Leu Arg Ser 1 i 220 225 230 1 1 1 本紙張尺度適用中國國家標準（CNS ) A4規格（21〇'乂297公釐） 127 3 8 0 7 6 538049 A7 B7 五、發明説明（1 28)Tyr Asp Gla G1 a Thr Ser His GIn Lea Lea Cys Asp Lys Cys Pro 10 15 20 This paper size applies to Chinese National Standard (CNS) A4 (210X297 mm) 126 3 8 0 7 6 538049 A7 B7 Central Bureau of Standards, Ministry of Economic Affairs Printed by the employee consumer cooperative V. Invention Description (1 27) 1 I Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 1 1 25 30 35 1 I Vai Cys Ala G1 u Cys Lys G lu Gly Arg Tyr Leu Glu Me Glu Phe 1 1 40 45 50 / ^ V Please 1 8 1 Cys Lea Lys His Arg Ser Cys Pro Pro Gly Phe Gly Vai Val Gin Reading 1 I 55 60 65 Back 1 I 1 Ala Gly Thr Pro G1 u Arg Asn Thr Vai Cys Lys Arg Cys Pro Asp Note 1 1 TO 75 80 Matters 1 IG ly Phe Phe Ser Asn GI u Thr Ser Ser Lys Ala Pro Cys Arg Lys Refill t 1 85 90 95 His Thr Asn Cys Ser Val Phe G on this page lv Leu Leu Lea Thr Gin Lys Gly 1 I 100 105 110 1 1 I Asn Ala Thr His Asp Asn I le Cys Ser Gly Asn Ser Gia Ser Thr 1 1 115 120 125 Order I Gin Lys Cys G 1 y [le Asp Val Thr Leu Cys G lu G lu Ala Phe Phe 1 1 130 135 140 1 I Arg Phe Ala Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val 1 1 145 150 155 4 Leu Val Asp Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val 1 I 160 165 170 1 1 G1 u Arg lie Lys Arg Gin His Ser Ser Gin Gla G 1 n Thr Phe Gin 1 I 175 180 185 1 1 Leu Leu Lys Lea Trp Lys His Gin Asn Lys Asp Gin Asp [le Val 1 I 190 195 200 1 1 Lys Lys He I le Gin Asp (le Asp Leu Cys G la Asn Ser Val Gin 1 I 205 210 215 1 1 Arg His I le Gly His Ala Asn Leu Thr Phe G la Gin Leu Arg Ser 1 i 220 225 230 1 1 1 This paper size applies to the Chinese National Standard (CNS) A4 size (21〇 '乂 297 mm) 127 3 8 0 7 6 538049 A7 B7 V. Description of Invention (1 28)

Leu Met Glu Ser Leu Pro Gly Lys Lys Val Gly Ala Glu Asp lie 235 240 245Leu Met Glu Ser Leu Pro Gly Lys Lys Val Gly Ala Glu Asp lie 235 240 245

Glu Lys Thr lie Lys Ala Cys Lys Pro Ser Asp Gin lie Leu Lys 250 255 260Glu Lys Thr lie Lys Ala Cys Lys Pro Ser Asp Gin lie Leu Lys 250 255 260

Lea Leu Ser Leu Trp Arg lie Lys Asn Gly Asp Gin Asp Thr Leu 265 270 275Lea Leu Ser Leu Trp Arg lie Lys Asn Gly Asp Gin Asp Thr Leu 265 270 275

Lys Gly Leu Met His Ala Leu Lys His Ser Lys Thr Tyr His Phe 280 285 290Lys Gly Leu Met His Ala Leu Lys His Ser Lys Thr Tyr His Phe 280 285 290

Pro Lys Thr Val Thr Gin Ser Leu Lys Lys Thr [le Arg Phe Leu 295 300 305Pro Lys Thr Val Thr Gin Ser Leu Lys Lys Thr [le Arg Phe Leu 295 300 305

His Ser Phe Thr Met Tyr Lys Leu Tyr Gin Lys Leu Phe Leu Glu 310 315 320His Ser Phe Thr Met Tyr Lys Leu Tyr Gin Lys Leu Phe Leu Glu 310 315 320

Met lie Gly Asn Gin Val Gin Ser Val Lys [le Ser Cys Leu 325 330 335 序列號碼：69 序列長度：363 序列型：胺基酸鏈數：1 局部解剖狀：直鐽狀序列種類：蛋白質（0CIF-DCR3) 序列：Met lie Gly Asn Gin Val Gin Ser Val Lys [le Ser Cys Leu 325 330 335 Sequence number: 69 Sequence length: 363 Sequence type: Amino acid chain number: 1 Local anatomy: Mullion sequence type: Protein (0CIF- DCR3) sequence:

Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 [le Lys Trp Thr Thr Gla Gla Thr Phe Pro Pro Lys Tyr Leu His (請先閱讀背面之注意事項再填寫本頁) -tr填寫太經濟部中央標準局員工消費合作社印製 -5 ] l 5 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 128 3 8 0 7 6 904 8 3 A7 五 _ B7 ____ 發明説明（l29) ^Vr Asp Gla Glu Thr Ser His Gin Lea Leu Cys Asp Lys Cys Pro l〇 15 20Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 [le Lys Trp Thr Thr Thr Gla Gla Thr Phe Pro Pro Lys Tyr Leu His (Please read the notes on the back before filling this page) -tr fill in printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs-5] l 5 This paper size applies to the Chinese National Standard (CNS) A4 specification (210X297 mm) 128 3 8 0 7 6 904 8 3 A7 five_ B7 ____ Description of the Invention (l29) ^ Vr Asp Gla Glu Thr Ser His Gin Lea Leu Cys Asp Lys Cys Pro 〇15 20

Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr (請先閱讀背面之注意事項再填寫本頁) 25 30 35Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr (Please read the notes on the back before filling this page) 25 30 35

Thr Ser Asp Glu Cys Lea Tyr Cys Ser Pro Val Cys Lys Gla Lea 55 60 65Thr Ser Asp Glu Cys Lea Tyr Cys Ser Pro Val Cys Lys Gla Lea 55 60 65

Arg Cys Pro Asp Gly Phe Phe Ser Asn Gla Thr Ser Ser Lys Ala 85 90 95Arg Cys Pro Asp Gly Phe Phe Ser Asn Gla Thr Ser Ser Lys Ala 85 90 95

Pro Cys Arg Lys His Thr Asn Cys Ser Val Phe Gly Leu Lea Leu 100 105 110Pro Cys Arg Lys His Thr Asn Cys Ser Val Phe Gly Leu Lea Leu 100 105 110

Thr Gin Lys Gly Asn Ala Thr His Asp Asn lie Cys Ser Gly Asn 115 120 125Thr Gin Lys Gly Asn Ala Thr His Asp Asn lie Cys Ser Gly Asn 115 120 125

Ser Glu Ser Thr Gin Lys Cys Gly [le Asp Val Thr. Leu Cys Glu 130 135 140Ser Glu Ser Thr Gin Lys Cys Gly [le Asp Val Thr. Leu Cys Glu 130 135 140

Glu Ala Phe Phe Arg Phe Ala Val Pro Thr Lys Phe Thr Pro Asn 145 150 155 經濟部中央標準局員工消費合作社印製Glu Ala Phe Phe Arg Phe Ala Val Pro Thr Lys Phe Thr Pro Asn 145 150 155 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs

Trp Leu Ser Val Leu Vai Asp Asn Leu Pro Gly Thr Lys Val Asn 160 165 170Trp Leu Ser Val Leu Vai Asp Asn Leu Pro Gly Thr Lys Val Asn 160 165 170

Ala Glu Ser Val Glu Arg lie Lys Arg Gin His Ser Ser Gin Glu 175 180 185Ala Glu Ser Val Glu Arg lie Lys Arg Gin His Ser Ser Gin Glu 175 180 185

Gin Thr Phe Gin Leu Leu Lys Leu Trp Lys His Gin Asn Lys Asp 190 195 200Gin Thr Phe Gin Leu Leu Lys Leu Trp Lys His Gin Asn Lys Asp 190 195 200

Gin Asp lie Val Lys Lys lie lie Gin Asp lie Asp Leu Cys Gla 205 210 215 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 129 3 8 0 7 6 538049 A7 B7 五、發明説明（1 30)Gin Asp lie Val Lys Lys lie lie Gin Asp lie Asp Leu Cys Gla 205 210 215 This paper size applies to Chinese National Standard (CNS) A4 specification (210X297 mm) 129 3 8 0 7 6 538049 A7 B7 V. Description of the invention (1 30)

Asn Ser Val Gin Arg His lie Gly His Ala Asn Leu Thr Phe Glu 220 225 230Asn Ser Val Gin Arg His lie Gly His Ala Asn Leu Thr Phe Glu 220 225 230

Gin Leu Arg Ser Leu Met Glu Ser Leu Pro Gly Lys Lys Val Gly 235 240 245Gin Leu Arg Ser Leu Met Glu Ser Leu Pro Gly Lys Lys Val Gly 235 240 245

Ala Glu Asp lie Glu Lys Thr lie Lys Ala Cys Lys Pro Ser Asp 250 255 260Ala Glu Asp lie Glu Lys Thr lie Lys Ala Cys Lys Pro Ser Asp 250 255 260

Gln lie Leu Lys Leu Leu Ser Leu Trp Arg Ile Lys Asn Gly Asp 265 270 275Gln lie Leu Lys Leu Leu Ser Leu Trp Arg Ile Lys Asn Gly Asp 265 270 275

Gin Asp Thr Leu Lys Gly Leu Met His Ala Leu Lys His Ser Lys 280 285 290Gin Asp Thr Leu Lys Gly Leu Met His Ala Leu Lys His Ser Lys 280 285 290

Thr Tyr His Phe Pro Lys Thr Val Thr Gin Ser Leu Lys Lys Thr 295 300 305 [le Arg Phe Lea fits Ser Phe Thr (let Tyr Lys Leu Tyr Gin Lys 310 315 320Thr Tyr His Phe Pro Lys Thr Val Thr Gin Ser Leu Lys Lys Thr 295 300 305 [le Arg Phe Lea fits Ser Phe Thr (let Tyr Lys Leu Tyr Gin Lys 310 315 320

Leu Phe Leu Glu ilet [le Gly Asn Gin Val Gin Ser Val Lys He 325 330 335Leu Phe Leu Glu ilet [le Gly Asn Gin Val Gin Ser Val Lys He 325 330 335

Ser Cys Leu 340 經濟部中央標準局員工消費合作社印製 (請先閲讀背面之注意事項再填寫本頁) 序列號碼：70 序列長度：3 5 9 序列型：胺基酸鏈數：1 局部解剖狀：直鏈狀序列種類：蛋白質（0CIF-DCR4) 序列：本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 130 3 8 0 7 6 538049 A7 —_____ B7 _ 五、發明説明（1 3 1)Ser Cys Leu 340 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (please read the notes on the back before filling out this page) Serial Number: 70 Sequence Length: 3 5 9 Sequence Type: Amino Acid Chain: 1 Local Anatomy ： Straight chain type ： Protein （0CIF-DCR4） Sequence ： This paper size is applicable to Chinese National Standard (CNS) A4 (210X 297 mm) 130 3 8 0 7 6 538049 A7 —_____ B7 _ V. Description of the invention 1 3 1)

Met Asn Asn Lea Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Gla Thr Phe Pro Pro Lys Tyr Leu His -5 -11 5Met Asn Asn Lea Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Gla Thr Phe Pro Pro Lys Tyr Leu His -5 -11 5

Tyr Asp Gla Gla Thr Ser His G1 a Leu Leu Cys Asp Lys Cys Pro 10 15 20Tyr Asp Gla Gla Thr Ser His G1 a Leu Leu Cys Asp Lys Cys Pro 10 15 20

Thr Ser Asp Gla Cys Lea Tyr Cys Ser Pro Val Cys Lys Glu Lea 55 60 65Thr Ser Asp Gla Cys Lea Tyr Cys Ser Pro Val Cys Lys Glu Lea 55 60 65

Glu Cys Lys Glu Gly Arg Tyr Lea Glu lie Glu Phe Cys Leu Lys 85 90 95Glu Cys Lys Glu Gly Arg Tyr Lea Glu lie Glu Phe Cys Leu Lys 85 90 95

Pro Glu Arg Asn Thr Val Cys Lys Ser Gly Asn Ser Glu Ser Thr 115 120 125 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁)Pro Glu Arg Asn Thr Val Cys Lys Ser Gly Asn Ser Glu Ser Thr 115 120 125 Printed by the Staff Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (Please read the notes on the back before filling out this page)

Gin Lys Cys Gly [le Asp Val Thr Leu Cys Glu Glu Ala Phe Phe 130 135 140Gin Lys Cys Gly [le Asp Val Thr Leu Cys Glu Glu Ala Phe Phe 130 135 140

Arg Phe Ala Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val 145 150 155Arg Phe Ala Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val 145 150 155

Leu Val Asp Asn Lea Pro Gly Thr Lys Val Asn Ala Glu Ser Val 160 165 170Leu Val Asp Asn Lea Pro Gly Thr Lys Val Asn Ala Glu Ser Val 160 165 170

Glu Arg lie Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe Gin 175 130 185 本紙張尺度適用中國國家標準（CNS ) A4規格（210Χ2·97公釐） 131 38076 538049 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明（13 2)Glu Arg lie Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe Gin 175 130 185 This paper size applies to Chinese National Standard (CNS) A4 (210 × 2 · 97 mm) 131 38076 538049 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention (13 2)

Leu Lea Lys Leu Trp Lys His Gin Asn Lys Asp Gin Asp [le Val 190 195 200Leu Lea Lys Leu Trp Lys His Gin Asn Lys Asp Gin Asp [le Val 190 195 200

Lys Lys lie lie Gin Asp lie Asp Leu Cys Glu Asn Ser Valt Gin 205 210 215Lys Lys lie lie Gin Asp lie Asp Leu Cys Glu Asn Ser Valt Gin 205 210 215

Arg His [le Gly His Ala Asn Leu Thr Phe Glu Gin Leu Arg Ser 220 225 230Arg His [le Gly His Ala Asn Leu Thr Phe Glu Gin Leu Arg Ser 220 225 230

Lea Leu Ser Leu Trp Arg lie Lys Asn Gly Asp Gin Asp Thr Lea 265 270 275Lea Leu Ser Leu Trp Arg lie Lys Asn Gly Asp Gin Asp Thr Lea 265 270 275

Pro Lys Thr Val Thr Gin Ser Leu Lys Lys Tfir He Arg Phe Leu 295 300 305Pro Lys Thr Val Thr Gin Ser Leu Lys Lys Tfir He Arg Phe Leu 295 300 305

His Ser Phe Thr ilet Tyr Lys Lea Tyr Gin Lys Leu Phe Leu Glu 310 315 320His Ser Phe Thr ilet Tyr Lys Lea Tyr Gin Lys Leu Phe Leu Glu 310 315 320

Met [le Gly Asn Gin Val Gin Ser Val Lys lie Ser Cys Leu 325 330 335 序列號碼：7 1 序列長度：326 序列型：胺基酸鐽數：1 局部解剖狀：直鐽狀序列種類：蛋白質（0CIF-DDD1) 序列：本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐）工3 2 3 8 0 7 6 (請先閱讀背面之注意事項再填寫本頁) _ 、11 538049 A7 —______ B7 五、發明説明（13 3)Met [le Gly Asn Gin Val Gin Ser Val Lys lie Ser Cys Leu 325 330 335 Sequence Number: 7 1 Sequence Length: 326 Sequence Type: Amino Acid Number: 1 Local Anatomy: Orthogonal Sequence Type: Protein (0CIF -DDD1) Sequence: This paper size applies to Chinese National Standard (CNS) A4 specification (210X297 mm) 3 2 3 8 0 7 6 (Please read the notes on the back before filling this page) _ 、 11 538049 A7 —______ B7 V. Description of Invention (13 3)

Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Lea Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Lea His -5 -11 5Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Lea Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Lea His -5 -11 5

Tyr Asp Glu Glu Thr Ser His Gin Lea Leu Cys Asp Lys Cys Pro 10 15 20Tyr Asp Glu Glu Thr Ser His Gin Lea Leu Cys Asp Lys Cys Pro 10 15 20

Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp S'er Trp His 40 45 50Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp S'er Trp His 40 45 50

Glu Cys Lys Glu Gly Arg Tyr Leti Glu [le Glu Phe Cys Leu Lys 85 90 95Glu Cys Lys Glu Gly Arg Tyr Leti Glu [le Glu Phe Cys Leu Lys 85 90 95

His Arg Ser Cys Pro Pro Gly Phe Gly Vat Val Gin Ala Gly Thr 100 105 110His Arg Ser Cys Pro Pro Gly Phe Gly Vat Val Gin Ala Gly Thr 100 105 110

Pro Glu Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 115 120 125 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁)Pro Glu Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 115 120 125 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (Please read the notes on the back before filling out this page)

Ser Asn Glu Thr Ser Ser Lys A1 a Pro Cys Arg Lys His Thr Asn 130 135 140Ser Asn Glu Thr Ser Ser Lys A1 a Pro Cys Arg Lys His Thr Asn 130 135 140

Cys Ser Val Phe Gly Leu Leu Leu Thr Gin Lys Gly Asn A la Thr 145 150 155Cys Ser Val Phe Gly Leu Leu Leu Thr Gin Lys Gly Asn A la Thr 145 150 155

Hi5 Asp Asn [le Cys Ser Gly Asn Ser Glu Ser Thr G1n Lys Cys 160 L65 170Hi5 Asp Asn [le Cys Ser Gly Asn Ser Glu Ser Thr G1n Lys Cys 160 L65 170

Gly [le Asp [le Asp Leu Cys Glu Asn Ser Val Gin Arg His lie 175 180 135 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 133 3 8 0 7 6 538049 A7 B7 經濟部中央標準局員工消費合作社印製五、發明説明（！34) 1 1 Gly His Ala Asn Leu Thr Phe G1 u Gin Leu Arg Ser Leu Me t G l u 1 I 190 195 200 1 1 Ser Lea Pro Gly Lys Lys Val Gly Ala Gla Asp I le G1 u Lys Thr 1 I 205 210 215 請先 1 1 lie Lys Ala Cys Lys Pro Ser Asp Gin He Leu Lys Leu Leu Ser Η 讀背 1 | 220 225 230 rj 之 1 Lea Trp Arg lie Lys Asn Gly Asp Gin Asp Thr Leu Lys Gly Leu 注意事 1 1 235 240 245 再 1 4 I Met His Ala Leu Lys His Ser Lys Thr Tyr His Phe Pro Lys Thr 填寫本 250 255 260 頁、W〆 1 I Val Thr Gin Ser Leu Lys Lys Thr I ie Arg Phe Leu His Ser Phe 1 1 265 270 275 1 I Thr fie t Tyr Lys Leu Tyr Gin Lys Leu Phe Leu Gia !1e t i Ie Gly 1 訂 1 230 285 290 Asn Gin Vai Gin Ser Val Lys lie Ser Cys Leu 1 I 295 300 305 1 1 I 序列 M 碼： 72 1 序列長度： 327 1 I 序列型 :胺基酸 1 1 I 鏈數 • 1 1 1 局部解剖狀 * 直a 丨狀 1 1 序列種類：蛋白質（〇C IF -DDD2) 1 1 序列： 1 As η As η Leu Leu Cys Cys Ala Leu VaL Phe Leu Asp I le Ser 1 I -20 -15 -10 1 1 He Lys Trp Thr Thr Gin GU Thr Phe Pro Pro Lys Tyr Leu His 1 I -5 -1 1 5 隹 1 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 38076 538049 A7 B7 五、發明説明（l35)Gly [le Asp [le Asp Leu Cys Glu Asn Ser Val Gin Arg His lie 175 180 135 This paper size applies to the Chinese National Standard (CNS) A4 size (210X297 mm) 133 3 8 0 7 6 538049 A7 B7 Central Standard of the Ministry of Economy Printed by the Bureau ’s Consumer Cooperatives V. Invention Description (! 34) 1 1 Gly His Ala Asn Leu Thr Phe G1 u Gin Leu Arg Ser Leu Me t G lu 1 I 190 195 200 1 1 Ser Lea Pro Gly Lys Lys Val Gly Ala Gla Asp I le G1 u Lys Thr 1 I 205 210 215 Please first 1 1 lie Lys Ala Cys Lys Pro Ser Asp Gin He Leu Lys Leu Leu Ser Η Read Back 1 | 220 225 230 rj 1 Lea Trp Arg lie Lys Asn Gly Asp Gin Asp Thr Leu Lys Gly Leu Note 1 1 235 240 245 Re 1 4 I Met His Ala Leu Lys His Ser Lys Thr Tyr His Phe Pro Lys Thr Fill in this 250 255 260 pages, W〆1 I Val Thr Gin Ser Leu Lys Lys Thr I ie Arg Phe Leu His Ser Phe 1 1 265 270 275 1 I Thr fie t Tyr Lys Leu Tyr Gin Lys Leu Phe Leu Gia! 1e ti Ie Gly 1 order 1 230 285 290 Asn Gin Vai Gin Ser Val Lys lie Ser Cys Leu 1 I 295 300 305 1 1 I sequence M code: 72 1 sequence length: 327 1 I sequence type: amino acid 1 1 I chain number • 1 1 1 Partial Anatomy * Straight a 丨 like 1 1 Sequence Type: Protein (〇C IF -DDD2) 1 1 Sequence: 1 As η As η Leu Leu Cys Cys Ala Leu VaL Phe Leu Asp I le Ser 1 I -20- 15 -10 1 1 He Lys Trp Thr Thr Gin GU Thr Phe Pro Pro Lys Tyr Leu His 1 I -5 -1 1 5 隹 1 This paper size applies to China National Standard (CNS) A4 (210X297 mm) 38076 538049 A7 B7 V. Description of Invention (l35)

Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Gla Lea 55 60 65Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Gla Lea 55 60 65

Gla Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80Gla Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80

Gla Cys Lys Glu Giy Arg Tyr Leu Glu lie Gla Phe Cys Lea Lys 85 90 95Gla Cys Lys Glu Giy Arg Tyr Leu Glu lie Gla Phe Cys Lea Lys 85 90 95

Cys Ser Val Phe Giy Leu Leu Leu Thr Gin Lys Gly Asa Ala Thr 145 150 155 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁)Cys Ser Val Phe Giy Leu Leu Leu Thr Gin Lys Gly Asa Ala Thr 145 150 155 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (Please read the notes on the back before filling out this page)

His Asp Asn lie Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Cys 160 165 170His Asp Asn lie Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Cys 160 165 170

Gly lie Asp Val Thr Leu Cys Glu Glu Ala Phe Phe Arg Phe Aia 175 180 185Gly lie Asp Val Thr Leu Cys Glu Glu Ala Phe Phe Arg Phe Aia 175 180 185

Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val Lea Val Asp 190 195 200Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val Lea Val Asp 190 195 200

Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg Me 205 210 215 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 135 3 8 0 7 6 538049 A7 B7 經濟部中央標準局員工消費合作社印製五、發明説明（136) 1 I Lys Arg Gin His Ser Ser Gin Giu Gin Thr Phe Gin Leu Leu Lys 讎 1 I 220 225 230 1 1 Leu Trp Lys His Gin Asn Lys Asp Gin Asp [le •Val Lys Lys lie 1 I 235 240 245 請 £ 1 1 閱 I I le Gin Asp Ala Leu Lys His Ser Lys Thr Tyr His Phe Pro Lys 讀背之 1 I 250 255 260 1 1 | Thr Val Thr Gin Ser Lea Lys Lys Thr I le Arg Phe Leu His Ser 意 I 事 1 265 270 275 項再填寫本頁 1 Phe Thr Met Tyr Lys Leu Tyr Gin Lys Leu Phe Leu Glu He t I le 4 280 285 290 1 I G1 y Asn Gin Val Gin Ser Val Lys [le Ser Cys Leu 1 1 295 300 305 1 1 I 序列贴碼： 73 1 訂 1 序列長度·· 399 1 1 序列型 :胺基酸 1 | 鐽數： 1 1 • 局部解剖狀 1 直鏈丨狀 1 I 序列種類：蛋白質 [(OCIF -CL) 1 1 I 序列： 1 1 I Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp Π e Ser 1 1 ^20 -15 -10 1 I [le Lys Trp Thr Thr Gin Gla Thr Phe Pro Pro Lys Tyr Lea His 1 1 -5 1 5 1 I Tyr Asp G ί u Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys P co 1 I 10 15 20 1 1 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 136 3 8 0 7 6 538049 A7 B7 經濟部中央標準局員工消費合作社印製五、發明説明（1 3 7) 1 I Pro Giy Thr Tyr Lea Lys Gla His Cys Thr Ala Lys Trp Lys Thr 1 1 25 30 35 1 I Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 1 1 40 45 50 請 1 I 先 1 Thr Ser Asp G lu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 閱讀 1 I 55 60 65 背 1 I 之 1 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 注意 1 I 70 75 80 事項 1 I G Ια Cys Lys Glu Gly Arg Tyr Leu Gia I le Gla Phe Cys Leu Lys 再填寫本頁 4 85 90 95 1 His Arg Ser Cys Pro Pro Gly Phe Gly Vai Val Gin Ala G ly Thr 1 I 100 105 110 1 1 I Pro G1 u Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 1 I 115 120 125 訂 I Ser Asn G l u Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 1 1 130 135 140 1 1 Cys Ser Val Phe Gly Leu Leu Lea Thr Gin Lys Gly i\sn A ta Thr 1 1 145 150 155 1 • His Asp Asn lie Cys Ser Gly Asn Ser Glu Ser Thr G l n Lys Cys 1 I 160 165 170 1 1 G l y lie Asp Val Thr Leu Cys Glu Glu Ala Phe Phe Arg Phe Ala 1 I 175 180 185 1 1 Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Vai Leu Val Asp 1 I 190 195 200 1 1 Asn Leu Pro G ly Thr Lys Val Asn Ala G 1 a Ser Val Glu Arg I ί e 1 I 205 210 215 1 1 I Lys Arg Gin His Ser Ser Gin G l u Gin Thr Phe Gin Leu Leu Lys 1 | 220 225 230 1 1 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 137 3 8 0 7 6 538049 A7 B7 經濟部中央標準局員工消費合作社印製五、發明説明 (138) Val Lys Lys Me 1 Leu Trp Lys His Gin Asn Lys Asp Gin Asp He 1 I 235 240 245 1 1 11 e Gin Asp [le Asp Leu Cys Gla Asn Ser Val Gin Arg His He 1 | 250 255 260 /s 1 I 請 1 I Gly His Ala Asn Leu Thr Phe Gla Gin Leu Arg Ser Leu Met Glu 先閱 1 I 265 270 275 讀背· Ί I Ser Leu Pro Gly Lys Lys Val Gly Ala G1 u Asp I le G1 u Lys Thr 之注 1 I 280 285 290 ..意事 1 項 1 lie Lys Ala Cys Lys Pro Ser Asp Gin He Leu Lys Leu Leu Ser 填 295 300 305 寫本頁 1 Leu Trp Arg lie Lys Asn Gly Asp GlrT Asp Thr Leu Lys Gly Leu 、〆 1 1 310 315 320 1 1 He t His Aia Leu Lys His Ser Lys Thr Tyr His Phe Pro Lys Thr 1 I 325 330 335 1 訂 Val Thr Gin Ser Leu Lys Lys Thr He Arg Phe Leu His Ser Phe 1 | 340 345 350 1 I Thr Met Ty r Lys Leu Tyr Gin Lys Leu Phe Leu Giu Me t [le Gly 1 1 355 360 365 1 Asn Gin Val Gin Ser Val Lys I le Ser 件 370 375 1 序列號碼： 7 4 1 I 序列長度： 351 1 1 I 序列型 :胺基酸 1 1 鏈數： 1 1 1 局部解剖狀：直鏈狀 1 1 序列種類：蛋白質（0C IF-CC) 1 1 序列： 1 1 1 本紙張尺度適用中國國家標率（CNS ) A4規格（210X297公釐） j 3 g 3 8 0 7 6 538049 A7 B7 經濟部中央標準局員工消費合作社印製五、發明説明（139) 1 I flet Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Lea Asp I le Ser 1 1 -20 -15 -10 1 I I le Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Lea His 1 1 -5 ] 1 5 請 1 I 先 1 Ty r Asp Gla Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 閲讀 1 1 10 15 20 背 1 I 1 I Pro Gly Thr Tyr Leu Lys Gla His Cys Thr Ala Lys Trp Lys Thr 意 1 I 25 30 35 事項 1 I Vai Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 再填寫本頁蜷 40 45 50 1 Thr Ser Asp Giu Cys Lea Tyr Cys Ser Pro Vai Cys Lys Giu Leu 1 I 55 60 65 1 1 I Gin Tyr Val Lys Gin Gla Cys Asn Arg Thr His Asn Arg Val Cys 1 I 70 75 80 訂 | Gla Cys Lys G 1 a Gly Arg Tyr Leu G l a [le G I u Phe Cys Lea Lys 1 1 85 90 95 1 I His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Gly Thr 1 1 100 Glu 105 110 Pro Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 1 I ή 5 120 125 1 1 Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 1 1 130 135 140 1 1 Cys Ser Val Phe Gly Leu Leu Leu Thr Gin Lys Gly Asn Ala Thr 1 145 150 155 1 1 His Asp Asn I le Cys Ser Gly Asn Ser Gia Ser Thr Gin Lys Cys 1 I 160 165 170 1 1 G 1 y He Asp Val Thr Leu Cys G l a Glu Ala Phe Phe Arg Phe Ala 1 I 175 180 135 1 1 1 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 1 3 9 3 8 076 538049 A7 B7 經濟部中央標準局員工消費合作社印製五、發明説明（140) 1 1 Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val Leu Val Asp 1 I 190 195 200 1 1 Asn Lea Pro Gly Thr Lys Vai Asn Ala G l u Ser Val Glu Arg Ile /^、 1 I 205 .210 215 請 £ 1 1 閱 I Lys Arg Gin His Ser Ser Gin G l a Gin Thr Phe Gin Leu Leu Lys 讀背 1 | 220 225 230 面之 1 注 I Leu Trp Lys His Gin Asn Lys Asp Gin Asp lie Vai Lys Lys He 意事 1 235 240 245 項 1 lie Gin Asp lie Asp Leu Cys G1 a Asn Ser Val Gin Arg His lie 丹填寫本 4 250 255 260 頁 1 I Gly His Ala Asn Leu Thr Phe Gia Gin Leu Arg Ser Leu ile t Glu 1 265 270 275 1 I Ser Leu Pro Gly Lys Lys Val Gly Ala G l u Asp I te Glu Lys Thr 1 1 訂 | 230 285 290 11 e Lys Ala Cys Lys Pro Ser Asp Gin [le Leu Lys Leu Leu Ser 295 300 305 1 1 Leu Trp Arg He Lys Asn Gly Asp Gin A.sp Thr Lea L y Gly Leu 1 I 310 315 320 • Me t His Ala Leu Lys His 325 330 1 1 1 序列號碼 ·· 75 1 1 1 序列長度：272 1 1 序列型胺基酸 1 I 鐽數： 1 1 1 I 局部解剖狀：直鏈狀 1 1 序列種類 :蛋白質（0C IF-CDD2) 1 1 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 14〇 38076 538049 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明（1 41) 序列：Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg Me 205 210 215 This paper size applies to China National Standard (CNS) A4 (210X297 mm) 135 3 8 0 7 6 538049 A7 B7 Employees of the Central Bureau of Standards, Ministry of Economic Affairs Printed by a consumer cooperative V. Description of the invention (136) 1 I Lys Arg Gin His Ser Ser Gin Giu Gin Thr Phe Gin Leu Leu Lys 雠 1 I 220 225 230 1 1 Leu Trp Lys His Gin Asn Lys Asp Gin Asp [le • Val Lys Lys lie 1 I 235 240 245 Please £ 1 1 Read II le Gin Asp Ala Leu Lys His Ser Lys Thr Tyr His Phe Pro Lys Read Back 1 I 250 255 260 1 1 | Thr Val Thr Gin Ser Lea Lys Lys Thr I le Arg Phe Leu His Ser I I 1 265 270 275 items to fill out this page 1 Phe Thr Met Tyr Lys Leu Tyr Gin Lys Leu Phe Leu Glu He t I le 4 280 285 290 1 I G1 y Asn Gin Val Gin Ser Val Lys [le Ser Cys Leu 1 1 295 300 305 1 1 I Serial number: 73 1 Order 1 Sequence length ·· 399 1 1 Sequence type: Amino acid 1 | Number of loops: 1 1 • Topographic anatomy 1 Straight chain 丨 like 1 I Sequence type: protein [(OCIF -CL) 1 1 I sequence: 1 1 I Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp Π e Ser 1 1 ^ 20 -15 -10 1 I [le Lys Trp Thr Thr Gin Gla Thr Phe Pro Pro Lys Tyr Lea His 1 1 -5 1 5 1 I Tyr Asp G ί u Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys P co 1 I 10 15 20 1 1 This paper size applies to China National Standard (CNS) A4 (210X297 mm) 136 3 8 0 7 6 538049 A7 B7 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs V. Invention Description (1 3 7) 1 I Pro Giy Thr Tyr Lea Lys Gla His Cys Thr Ala Lys Trp Lys Thr 1 1 25 30 35 1 I Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 1 1 40 45 50 Please 1 I first 1 Thr Ser Asp G lu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu Read 1 I 55 60 65 Back 1 I of 1 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys Note 1 I 70 75 80 Matter 1 IG Ια Cys Lys Glu Gly Arg Tyr Leu Gia I le Gla Phe Cys Leu Lys Refill this page 4 85 90 95 1 His Arg Ser Cys Pro Pro Gly Phe Gly Vai Val Gin Ala G ly Thr 1 I 100 105 110 1 1 I Pro G1 u Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 1 I 115 120 125 Order I Ser Asn G lu Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 1 1 130 135 140 1 1 Cys Ser Val Phe Gly Leu Leu Lea Thr Gin Lys Gly i \ sn A ta Thr 1 1 145 150 155 1 • His Asp Asn lie Cys Ser Gly Asn Ser Glu Ser Thr G ln Lys Cys 1 I 160 165 170 1 1 G ly lie Asp Val Thr Leu Cys Glu Glu Ala Phe Phe Arg Phe Ala 1 I 175 180 185 1 1 Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Vai Leu Val Asp 1 I 190 195 200 1 1 Asn Leu Pro G ly Thr Lys Val Asn Ala G 1 a Ser Val Glu Arg I ί e I 205 210 215 1 1 I Lys Arg Gin His Ser Ser Gin G lu Gin Thr Phe Gin Leu Leu Lys 1 | 220 225 230 1 1 This paper size is applicable to Chinese National Standard (CNS) A4 (210X 297 mm) 137 3 8 0 7 6 538049 A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (138) Val Lys Lys Me 1 Leu Trp Lys His Gin Asn Lys Asp Gin Asp He 1 I 235 240 245 1 1 11 e Gin Asp [le Asp Leu Cys Gla Asn Ser Val Gin Arg His He 1 | 250 255 260 / s 1 I Please 1 I Gly His Ala Asn Leu Thr Phe Gla Gin Leu Arg Ser Leu Met Glu Read First 1 I 265 270 275 Read Back · Ί I Ser Leu Pro Gly Lys Lys Val Gly Ala G1 u Asp I le G1 u Lys Thr Note 1 I 280 285 290: 1 item 1 lie Lys Ala Cys Lys Pro Ser Asp Gin He Leu Lys Leu Leu Ser Fill 295 300 305 Write Page 1 Leu Trp Arg lie Lys Asn Gly Asp GlrT Asp Thr Leu Lys Gly Leu, 〆1 1 310 315 320 1 1 He t His Aia Leu Lys His Ser Lys Thr Tyr His Phe Pro Lys Thr 1 I 325 330 335 1 Order Val Thr Gin Ser Leu Lys Lys Thr He Arg Phe Leu His Ser Phe 1 | 340 345 350 1 I Thr Met Ty r Lys Leu Tyr Gin Lys Leu Phe Leu Giu Me t [le Gly 1 1 355 360 365 1 Asn Gin Val Gin Ser Val Lys I le Ser piece 370 375 1 sequence number: 7 4 1 I sequence length: 351 1 1 I sequence type: amino acid 1 1 chain number: 1 1 1 local anatomy: linear 1 1 sequence type: Protein (0C IF-CC) 1 1 Sequence: 1 1 1 This paper size applies to China National Standard (CNS) A4 specifications (210X297 mm) j 3 g 3 8 0 7 6 538049 A7 B7 Staff Consumption of Central Standards Bureau, Ministry of Economic Affairs Printed by the cooperative V. Description of the invention (139) 1 I flet As n Asn Leu Leu Cys Cys Ala Leu Val Phe Lea Asp I le Ser 1 1 -20 -15 -10 1 II le Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Lea His 1 1 -5] 1 5 Please 1 I First 1 Ty r Asp Gla Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro Read 1 1 10 15 20 Back 1 I 1 I Pro Gly Thr Tyr Leu Lys Gla His Cys Thr Ala Lys Trp Lys Thr Italian 1 I 25 30 35 Matter 1 I Vai Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His Refill this page 蜷 40 45 50 1 Thr Ser Asp Giu Cys Lea Tyr Cys Ser Pro Vai Cys Lys Giu Leu 1 I 55 60 65 1 1 I Gin Tyr Val Lys Gin Gla Cys Asn Arg Thr His Asn Arg Val Cys 1 I 70 75 80 Order | Gla Cys Lys G 1 a Gly Arg Tyr Leu G la [le GI u Phe Cys Lea Lys 1 1 85 90 95 1 I His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Gly Thr 1 1 100 Glu 105 110 Pro Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 1 I Price 5 120 125 1 1 Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 1 1 130 135 140 1 1 Cys Ser Val Phe Gly Leu Leu Leu Thr Gin Lys Gly Asn Ala Thr 1 145 150 155 1 1 His Asp Asn I le Cys Ser Gly Asn Ser Gia Ser Thr Gin Lys Cys 1 I 160 165 170 1 1 G 1 y He Asp Val Thr Leu Cys G la Glu Ala Phe Phe Arg Phe Ala 1 I 175 180 135 1 1 1 This paper size applies China National Standard (CNS) A4 specification (210X297 mm) 1 3 9 3 8 076 538049 A7 B7 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (140) 1 1 Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val Leu Val Asp 1 I 190 195 200 1 1 Asn Lea Pro Gly Thr Lys Vai Asn Ala G lu Ser Val Glu Arg Ile / ^, 1 I 205 .210 215 Please £ 1 1 Read I Lys Arg Gin His Ser Ser Gin G la Gin Thr Phe Gin Leu Leu Lys Read Back 1 | 220 225 230 Face 1 Note I Leu Trp Lys His Gin A sn Lys Asp Gin Asp lie Vai Lys Lys He Meaning 1 235 240 245 Items 1 lie Gin Asp lie Asp Leu Cys G1 a Asn Ser Val Gin Arg His lie Dan fill in this 4 250 255 260 page 1 I Gly His Ala Asn Leu Thr Phe Gia Gin Leu Arg Ser Leu ile t Glu 1 265 270 275 1 I Ser Leu Pro Gly Lys Lys Val Gly Ala G lu Asp I te Glu Lys Thr 1 1 Order | 230 285 290 11 e Lys Ala Cys Lys Pro Ser Asp Gin [le Leu Lys Leu Leu Ser 295 300 305 1 1 Leu Trp Arg He Lys Asn Gly Asp Gin A.sp Thr Lea L y Gly Leu 1 I 310 315 320 • Me t His Ala Leu Lys His 325 330 1 1 1 serial number ·· 75 1 1 1 Sequence length: 272 1 1 Sequence type amino acid 1 I Number of loops: 1 1 1 I Local anatomy: linear 1 1 Sequence type: protein (0C IF-CDD2) 1 1 paper size Applicable to China National Standard (CNS) A4 specification (210X297mm) 14〇380 76 538049 Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs A7 B7 V. Description of Invention (1 41) Sequence:

Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp [le Ser -20 -15 -10 [te Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 -1 1 5Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp [le Ser -20 -15 -10 [te Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 -1 1 5

Tyr Asp Glu Glu Thr Ser His Gin Lea Lea Cys Asp Lys Cys Pro 10 15 20Tyr Asp Glu Glu Thr Ser His Gin Lea Lea Cys Asp Lys Cys Pro 10 15 20

Glu Cy-s Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Leu Lys 85 90 95Glu Cy-s Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Leu Lys 85 90 95

Ills Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Gly Thr 100 105 110Ills Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Gly Thr 100 105 110

Cys Ser Val Phe Gly Leu Leu Leu Thr Gin Lys Gly Λ^η Ala Thr 145 150 155Cys Ser Val Phe Gly Leu Leu Leu Thr Gin Lys Gly Λ ^ η Ala Thr 145 150 155

His Asp Asn lie Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Cys 160 [65 170 (請先閲讀背面之注意事項再填寫本頁) 訂本紙張尺度適用中國國家標準（CNS ) Α4規格（210X297公釐） 141 3 8 0 7 6 538049 A7 B7 五發明武明（l42) Giy lie Asp Val Thr Leu Cys Gla Glu Ala Phe Phe Arg Phe Ala 175 180 185 Val Pro Thr Lys Phe Thr Pro A^a Trp Leu Ser Val Leu Val A^p 190 195 200 Asa Leu Pro Gly Thr Lys Val Asn Ala Gla Ser Val Glu Arg [le 205 210 215 Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe Gin Leu Leu Lys 220 225 230 Leu Trp Lys His Gla Asn Lys Asp Gin Asp lie Val Lys Lys [le 235 240 [le Gin 250 序列號碼：76 序列長度：1 9 7 序列型：胺基酸鏈數：1局部解剖狀：直鏈狀序列種類：蛋白質（〇 C I F - C D D 1 ) 245 (請先閱讀背面之注意事項再填寫本頁) 訂His Asp Asn lie Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Cys 160 [65 170 (Please read the notes on the back before filling out this page) The size of the paper is applicable to the Chinese National Standard (CNS) Α4 specification (210X297 mm) 141 3 8 0 7 6 538049 A7 B7 Wu Ming (l42) Giy lie Asp Val Thr Leu Cys Gla Glu Ala Phe Phe Arg Phe Ala 175 180 185 Val Pro Thr Lys Phe Thr Pro A ^ a Trp Leu Ser Val Leu Val A ^ p 190 195 200 Asa Leu Pro Gly Thr Lys Val Asn Ala Gla Ser Val Glu Arg [le 205 210 215 Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe Gin Leu Leu Lys 220 225 230 Leu Trp Lys His Gla Asn Lys Asp Gin Asp lie Val Lys Lys [le 235 240 [le Gin 250 sequence number: 76 sequence length: 1 9 7 sequence type: amino acid chain number: 1 local anatomy: linear sequence type: protein (〇CIF-CDD 1) 245 (Please read the notes on the back before filling this page) Order

Met Asn Asn Leu Leu Cys Cys Ala Leu Val 卩he Leu Asp He Ser ^20 -15 -10 經濟部中央標準局員工消費合作社印製 [le Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 -1 1 5Met Asn Asn Leu Leu Cys Cys Ala Leu Val 卩 he Leu Asp He Ser ^ 20 -15 -10 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs [le Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 -1 1 5

Tyr Asp Glu Glu Thr Ser H is Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20Tyr Asp Glu Glu Thr Ser H is Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20

Pro G[y Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35Pro G [y Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35

Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 本紙張尺度適用中國國家標準（CNS ) Α4規格（210 X 297公釐） 142 3 8 0 7 6 538049 A7 B7 經濟部中央標準局員工消費合作社印製五、發明説明 (143) 1 1 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 1 1 55 60 65 1 I Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 1 I 請 1 I 70 75 80 先閱 1 | G1 α Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Lea Lys 讀背 1 面 I 85 90 95 之注 1 I His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Gly Thr 意事 1 項 | 100 105 110 再填 — Pro Glu Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 寫本頁 1 115 120 125 1 Ser Asn G l a Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 1 I 130 135 140 1 1 Cys Ser Val Phe Gly Lea Lea Lea Thr Gin Lys Gly Asn Ala Thr 1 訂 1 I 145 150 155 His Asp Asn He Cys Ser Giy Asn Ser Glu Ser Thr Gin Lys Cys 1 1 160 165 170 1 G ly [l.e 1 | 175 序列號碼： 77 1 1 I 序列長度： 143 1 1 序列型 ·♦胺基酸 1 1 鐽數 ·· 1 1 1 局部解剖狀直鏈狀 1 I 序列種類：蛋白質（OCIF '-CCR4) 1 I 序列 : 1 1 1 1 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 143 3 8 07 6 538049 Α7 Β7 經濟部中央標準局員工消費合作社印製五、發明説明（144) 1 1 Met Asn Asa Leu Lea Cys Cys Ala Leu Val Phe Lea Asp I le Ser 1 1 -20 -15 -10 1 I lie Lys Trp Thr Thr Gin G1 u Thr Phe Pro Pro Lys Tyr Leu His 1 1 -5 -1 1 5 -V 請 1 I 1 Ty r Asp G1 u G i u Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 閱讀 1 10 15 20 t 面 1 1 5 1 Pro G1 y Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 意 1 I 25 30 35 事項 1 I Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 再填寫 # 1 40 45 50 本頁 Thr Ser Asp Gla Cys Lea Tyr Cys Ser Pro Va 1 Cys Lys Glu Leu 、〆 1 I 55 60 65 1 1 Gin Tyr Val Lys Gin G lu Cys Asn Arg Thr His Asn Arg Val Cys 1 I 70 75 80 1 訂 I G ί u Cys Lys Gla G ly Arg Tyr Leu G1 u lie Glu Phe Cys Leu Lys 1 I 85 90 95 1 I His Arg Ser Cys Pro Pro G ly Phe G ly Val Val Gin Ala G l y Thr 1 1 100 105 110 1 • Pro G l u Arg Asn Thr Val Cys Lys 115 120 1 1 序列號碼·· 78 1 1 序列長度： 106 1 1 序列型：胺 :基酸 1 1 鏈數： 1 1 | 局部解剖狀：直鏈狀 1 I 序列種類：蛋白質（OC IF-CCR3) 1 1 I 序列： 1 1 本紙張尺度適用中國國家標準（CNS ) A4規格（210 X 297公釐） 144 3 8 0 7 6 538049 A7 B7 經濟部中央標準局員工消費合作社印製五、發明説明（1 4 5) 1 1 Met Asn Asn Leu Lea Cys Cys Ala Lea Val Phe Leu Asp [l e Ser 1 I -20 -15 -10 I 1 [le Lys Trp Thr Thr Gin G1 a Thr Phe Pro Pro Lys Tyr Leu His -N 1 | -5 -1 1 5 請先 1 1 閱 | Tyr Asp Glu Glu Thr Ser His Gin Leu Lea Cys Asp Lys Cys Pro 讀背 1 10 15 20 面之 1 注 1 Pro G ly Thr Tyr Leu Lys Gla His Cys Thr Ala Lys Trp Lys Thr 意事 1 25 30 35 項再 1 4 Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 寫本 40 45 50 頁、^〆 1 I Thr Ser Asp Glu Cys Lea Tyr Cys Ser Pro Vai Cys Lys Glu Leu 1 55 60 65 1 1 Gin Tyr Vai Lys Gin G1 u Cys Asn Arg Thr His Asn Arg Val, Cys 1 訂 70 75 80 1 G 1 u 1 I 85 1 1 I 序列號碼： 79 1 1 • 序列長度： 393 Τ I 序列型：胺 :基酸 1 1 I 局部解剖狀：直鏈狀 1 1 I 序列種類：蛋白質（0C IF-CBst) 1 1 序列： 1 1 Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp [le Ser 1 I -20 -[5 -10 1 1 fie Lys Trp Thr Thr Gin G 1 u Thr Phe Pro Pro Lys Tyr Leu His 1 I -5 -1 1 5 1 1 1 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 145 3 8 0 7 6 538049 Α7 Β7 經濟部中央標準局員工消費合作社印製五、發明説明（I46) 1 | Tyr Asp Glu G1 u Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 1 I 10 15 20 1 I Pro G ly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 1 1 25 30 35 /-s 請 1 I Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 先閱讀 1 1 40 45 50 背面 1 I Thr 55 Ser Asp Glu Cys Leu 60 Tyr Cys Ser Pro Val 65 Cys Lys Glu Leu 之注意事項 1 1 1 1 Gin Tyr Val Lys Gin Glu Cys Asa Arg Thr His Asn Arg Val Cys 再填寫 # 1 70 75 80 本頁 G l u Cys Lys Glu G ly Arg Tyr Leu G1 u He Glu Phe Cys Leu Lys 1 I 85 90 95 1 1 His Arg Ser Cys Pro Pro Gly Phe Gly Vai Vai Gia Ala Gly Thr 1 I 100 105 110 1 訂 Pro G 1 u Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 1 | 115 120 125 1 Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr A ：3 n 1 1 130 Cys Ser Va l Phe Gly 135 Leu Leu Leu Thr Gin 140 Lys Gly Asn Ala Thr 1 • U5 150 155 1 1 His Asp Asn [[e Cys Ser Gly Asn Ser G l u Ser Thr G l n Lys Cys 1 I 160 [65 170 1 1 G 1 y He Asp Val Thr Leu Cys G l a Glu Ala Phe Phe Arg Phe Ala 1 I 175 130 185 1 1 1 Val Pro Thr Lys Phe Thr Pro Asa Trp Leu Ser Val Leu Val Asp 1 1 190 195 200 1 Asn Leu Pro G ly Thr Lys Val Asn Ala Glu Ser Val G l u Arg I le 1 1 205 210 2L5 1 1 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） i 4β 3 8 076 538049 A7 __B7 五、發明説明（147)Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 This paper size applies to Chinese National Standard (CNS) Α4 size (210 X 297 mm) 142 3 8 0 7 6 538049 A7 B7 Central Standard of the Ministry of Economic Affairs Printed by the Bureau's Consumer Cooperatives V. Invention Description (143) 1 1 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 1 1 55 60 65 1 I Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 1 I Please 1 I 70 75 80 Read First 1 | G1 α Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Lea Lys Read Back 1 Side I 85 90 95 Note 1 I His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Gly Thr Meaning 1 item | 100 105 110 Refill — Pro Glu Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe Write this page 1 115 120 125 1 Ser Asn G la Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 1 I 130 135 140 1 1 Cys Ser Val Phe Gly Lea Lea Lea Thr Gin Lys Gly Asn Ala Thr 1 Order 1 I 145 150 155 His Asp Asn He Cys Ser Giy Asn Ser Glu Ser Thr Gin Lys Cys 1 1 160 165 170 1 G ly [le 1 | 175 Sequence Number: 77 1 1 I Sequence length: 143 1 1 Sequence type · Amino acid 1 1 Number · 1 1 1 Local anatomy linear 1 I Sequence type: Protein (OCIF '-CCR4) 1 I Sequence: 1 1 1 1 This paper size applies to Chinese National Standard (CNS) A4 (210X 297 mm) 143 3 8 07 6 538049 Α7 Β7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (144) 1 1 Met Asn Asa Leu Lea Cys Cys Ala Leu Val Phe Lea Asp I le Ser 1 1 -20 -15 -10 1 I lie Lys Trp Thr Thr Gin G1 u Thr Phe Pro Pro Lys Tyr Leu His 1 1 -5 -1 1 5- V Please 1 I 1 Ty r Asp G1 u G iu Thr Ser Hi s Gin Leu Leu Cys Asp Lys Cys Pro Reading 1 10 15 20 t Face 1 1 5 1 Pro G1 y Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr Italian 1 I 25 30 35 Matter 1 I Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His Refill # 1 40 45 50 This page Thr Ser Asp Gla Cys Lea Tyr Cys Ser Pro Va 1 Cys Lys Glu Leu 〆 1 I 55 60 65 1 1 Gin Tyr Val Lys Gin G lu Cys Asn Arg Thr His Asn Arg Val Cys 1 I 70 75 80 1 Order IG ί u Cys Lys Gla G ly Arg Tyr Leu G1 u lie Glu Phe Cys Leu Lys 1 I 85 90 95 1 I His Arg Ser Cys Pro Pro G ly Phe G ly Val Val Gin Ala G ly Thr 1 1 100 105 110 1 • Pro G lu Arg Asn Thr Val Cys Lys 115 120 1 1 Sequence number · 78 1 1 Sequence length: 106 1 1 Sequence type: Amine: Group Acid 1 1 Number of chains: 1 1 | Local anatomy: linear 1 I Type: Protein (OC IF-CCR3) 1 1 I Sequence: 1 1 This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 144 3 8 0 7 6 538049 A7 B7 Employees of the Central Standards Bureau of the Ministry of Economic Affairs Printed by a consumer cooperative V. Description of the invention (1 4 5) 1 1 Met Asn Asn Leu Lea Cys Cys Ala Lea Val Phe Leu Asp [le Ser 1 I -20 -15 -10 I 1 [le Lys Trp Thr Thr Gin G1 a Thr Phe Pro Pro Lys Tyr Leu His -N 1 | -5 -1 1 5 Please read 1 1 first | Tyr Asp Glu Glu Thr Ser His Gin Leu Lea Cys Asp Lys Cys Pro Readback 1 10 15 20 Side 1 Note 1 Pro G ly Thr Tyr Leu Lys Gla His Cys Thr Ala Lys Trp Lys Thr Meaning 1 25 30 35 items and 1 4 Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Thr Asp Ser Trp His Manuscript 40 45 50 pages, ^ 〆1 I Thr Ser Asp Glu Cys Lea Tyr Cys Ser Pro Vai Cys Lys Glu Leu 1 55 60 65 1 1 Gin Tyr Vai Lys Gin G1 u Cys Asn Arg Thr His Asn Arg Val, Cys 1 Order 70 75 80 1 G 1 u 1 I 85 1 1 I sequence number: 79 1 1 • sequence length: 393 Τ I sequence type: amine: basic acid 1 1 I local anatomy: straight chain 1 1 I Sequence Type: Protein (0C IF-CBst) 1 1 Sequence: 1 1 Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp [le Ser 1 I -20-[5 -10 1 1 fie Lys Trp Thr Thr Thr Gin G 1 u Thr Phe Pro Pro Lys Tyr Leu His 1 I -5 -1 1 5 1 1 1 This paper size applies to China National Standard (CNS) A4 size (210X 297 mm) 145 3 8 0 7 6 538049 Α7 Β7 Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs. 5. Description of Invention (I46) 1 | Tyr Asp Glu G1 u Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 1 I 10 15 20 1 I Pro G ly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 1 1 25 30 35 / -s Please 1 I Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His Read 1 1 40 45 50 Back 1 I Thr 55 Ser Asp Glu Cys Leu 60 Tyr Cys Ser Pro Val 65 Cys Lys Glu Leu Notes 1 1 1 1 Gin Tyr Val Lys Gin Glu Cys Asa Arg Thr His Asn Arg Val Cys Refill # 1 70 75 80 This page G lu Cys Lys Glu G ly Arg Tyr Leu G1 u He Glu Phe Cys Leu Lys 1 I 85 90 95 1 1 His Arg Ser Cys Pro Pro Gly Phe Gly Vai Vai Gia Ala Gly Thr 1 I 100 105 110 1 Order Pro G 1 u Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 1 | 115 120 125 1 Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr A: 3 n 1 1 130 Cys Ser Va l Phe Gly 135 Leu Leu Leu Thr Gin 140 Lys Gly Asn Ala Thr 1 • U5 150 155 1 1 His Asp Asn [[e Cys Ser Gly Asn Ser G lu Ser Thr G ln Lys Cys 1 I 160 [65 170 1 1 G 1 y He Asp Val Thr Leu Cys G la Glu Ala Phe Phe Arg Phe Ala 1 I 175 130 185 1 1 1 Val Pro Thr Lys Phe Thr Pro Asa Trp Leu Ser Val Leu Val Asp 1 1 190 195 200 1 Asn Leu Pro G ly Thr Lys Val Asn Ala Glu Ser Val G lu Arg I le 1 1 205 210 2L5 1 1 This paper size applies to China National Standard (CNS) A4 (210X297 mm) i 4β 3 8 076 538049 A7 __B7 V. Description of the invention (147)

Leu Trp Lys His Gin Asn Lys Asp Gin Asp [le Val Lys Lys lie 235 240 245 lie Gin Asp lie Asp Leu Cys Glu Asn Ser Val Gin Arg His lie 250 255 260Leu Trp Lys His Gin Asn Lys Asp Gin Asp [le Val Lys Lys lie 235 240 245 lie Gin Asp lie Asp Leu Cys Glu Asn Ser Val Gin Arg His lie 250 255 260

Gly His Ala Asn Lea Thr Phe Gla Gin Leu Arg Ser Leu Met Glu 265 270 275Gly His Ala Asn Lea Thr Phe Gla Gin Leu Arg Ser Leu Met Glu 265 270 275

Ser Lea Pro Gly Lys Lys Val Giy Ala Glu Asp lie Glu Lys Thr 280 285 290 lie Lys Ala Cys Lys Pro Ser Asp Gin lie Leu Lys Lea Leu Ser 295 300 305Ser Lea Pro Gly Lys Lys Val Giy Ala Glu Asp lie Glu Lys Thr 280 285 290 lie Lys Ala Cys Lys Pro Ser Asp Gin lie Leu Lys Lea Leu Ser 295 300 305

Leu Trp Arg lie Lys Asn Gly Asp Gin Asp Thr Lea Lys Gly Leu 310 315 320Leu Trp Arg lie Lys Asn Gly Asp Gin Asp Thr Lea Lys Gly Leu 310 315 320

Val Thr Gin Ser Leu Lys Lys Thr [le Arg Phe Leu His Ser Phe 340 345 350Val Thr Gin Ser Leu Lys Lys Thr [le Arg Phe Leu His Ser Phe 340 345 350

Thr ilet Tyr Lys Leu Tyr Gin Lys Leu Phe Leu Glu Met [le Gly 355 360 365Thr ilet Tyr Lys Leu Tyr Gin Lys Leu Phe Leu Glu Met [le Gly 355 360 365

Asn Leu Val 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) 370 序列號碼：80 序列長度：3 2 1 序列型：胺基酸局部解剖狀：直鏈狀序列種類：蛋白質（0 C I F - C S p h ) 序列：本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 147 3 8 0 7 6 538049 A7 B7 經濟部中央標準局員工消費合作社印製五、發明説明 (148) 1 1 ilet Asa Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp I le Ser 1 I -20 -15 -10 1 1 I le Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His 1 I -5 -1 1 5 -V 1 I 請 1 I Ty r Asp G1 a G1 u Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 先閱 1 I 10 15 20 讀背 1 1 I Pro G ly Thr Tyr Leu Lys G 1 n His Cys Thr Ala Lys Trp Lys Thr 之注 1 I 25 30 35 意事 1 1 項 I Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 再蜷 40 45 50 填寫本頁 1 Thr Ser Asp G l a Cys Lea Tyr Cys Ser Pro Val Cys Lys Glu Leu 1 55 60 65 1 I Gin Tyr Val Lys Gin Glu Cys Asa Arg Thr His Asa Arg Vai Cys 1 1 70 75 80 1 訂 Glu Cys Lys Glu G l y Arg Tyr Leu Glu He G I u Phe Cys Leu Lys 1 85 90 95 1 1 H i s Arg Ser Cys Pro Pro G1 y Phe Giy Val Val Gin Ala Gly Thr 1 1 100 105 110 1 Pro G l u Arg Asn Thr Val Cys Lys Arg Cys Pro Asp G ly Phe Phe 115 120 125 1 I Ser Asn G 1 u Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 1 1 130 135 140 1 I Cys Ser Val Phe G ly Leu Leu Leu Thr Gin Lys G ly Asa Ala Thr 1 1 I 145 150 155 1 I II Ts Asp Asa He Cys Ser G ly Asn Ser Glu Ser Thr Gla Lys Cys 1 160 165 170 1 G l y lie Asp Val Thr Leu Cys G l a Glu Ala Phe Phe Arg Phe Ala 1 I 175 130 185 1 1 1 本紙張尺度適用中國國家標準（CNS)A4規格（210x297公釐） 148 3 8 0 7 6 538049 A7 經濟部中央標準局員工消費合作社印製 B7 _ 五、發明説明（151) Met Asn Asn Lea Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 -11 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Lea Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35 Vai Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Lea Tyr Lea VaI 55 60 序列號碼：8 3 序列長度：1206 序列型：核酸鏈數：1 局部解剖狀：直鏈狀序列種類：cDNA(0CIF-C19S) 序列： ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTCTTG 120 TGTiACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT. GTACAGCAAA GTGCAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 CTATACTGCrt GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCCAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA -360 CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 (請先閱讀背面之注意事項再填寫本頁)Asn Leu Val Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling this page) 370 Serial number: 80 Sequence length: 3 2 1 Sequence type: Amino acid local anatomy: straight chain Sequence Type: Protein (0 CIF-CS ph) Sequence: This paper size applies to China National Standard (CNS) A4 (210X297 mm) 147 3 8 0 7 6 538049 A7 B7 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs Description of the invention (148) 1 1 ilet Asa Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp I le Ser 1 I -20 -15 -10 1 1 I le Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His 1 I -5 -1 1 5 -V 1 I Please 1 I Ty r Asp G1 a G1 u Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro Read 1 I 10 15 20 Read back 1 1 I Pro G ly Thr Tyr Leu Lys G 1 n His Cys Thr Ala Lys Trp Lys Thr Note 1 I 25 30 35 Meaning 1 1 item I Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His Refill 40 45 50 Fill in this page 1 Thr Ser Asp G la Cys Lea Tyr Cys Ser Pro Val Cys Lys Glu Leu 1 55 60 65 1 I Gin Tyr Val Lys Gin Glu Cys Asa Arg Thr His Asa Arg Vai Cys 1 1 70 75 80 1 Order Glu Cys Lys Glu G ly Arg Tyr Leu Glu He GI u Phe Cys Leu Lys 1 85 90 95 1 1 H is Arg Ser Cys Pro Pro G1 y Phe Giy Val Val Gin Ala Gly Thr 1 1 100 105 110 1 Pro G lu Arg Asn Thr Val Cys Lys Arg Cys Pro Asp G ly Phe Phe 115 120 125 1 I Ser Asn G 1 u Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 1 1 130 135 140 1 I Cys Ser Val Phe G ly Leu Leu Leu Thr Gin Lys G ly Asa Ala Thr 1 1 I 145 150 155 1 I II Ts Asp Asa He Cys Ser G ly Asn Ser Glu Ser Thr Gla Lys Cys 1 160 165 170 1 G ly lie Asp Val Thr Leu Cys G la Glu Ala Phe Phe Arg Phe Ala 1 I 175 130 185 1 1 1 This paper size applies to China National Standard (CNS) A4 (210x297 mm) 148 3 8 0 7 6 538049 A7 Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs B7 _ V. Description of the invention (151) Met Asn Asn Len Lea Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20- 15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 -11 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Lea Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35 Vai Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Lea Tyr Lea VaI 55 60 Sequence number: 8 3 Sequence length: 1206 Sequence type: a nucleic acid strand number: 1 topographical shape: linear sequence type: cDNA (0CIF-C19S) sequence:. ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTCTTG 120 TGTiACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGCAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 CTATACTGCrt GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCAC C 300 CACAACCGCG TGTGCCAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA -360 CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 (Please read the notes on the back before filling this page)

本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 151 3 8 0 7 6 538049 A7 B7 五、發明説明（152) GTTTGCAAAA GATGTCCAGA TGGGTTCTTC TCAAATGAGA CGTCATCTAA AGCACCCTGT 480 AGAAAACACA CAAATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG AAATGCAACA 540 CACGACAACA TATGTTCCGG AAACAGTGAA TCAACTCAAA AftAGTGGAAT AGATGTTACC 600 CTGTGTGAGG AGGCATTCTT CAGGTTTGCT GTTCCTACAA AGTTTACGCC TAACTGGCTT 660 AGTGTCTTGG TAGACAATTT GCCTGGCACC AAAGTAAACG CAGAGAGTGT AGAGAGGATA 720 AAACGGCAAC ACAGCTCACA AGAACAGACT TTCCAGCTGC TGAAGTTATG GAAACATCAA 780 AACAAAGACC AAGATATAGT CAAGAAGATC ATCCAAGATA TTGACCTCTG TGAAAACAGC 840 GTGCAGCGGC ACATTGGACA TGCTAACCTC ACCTTCGAGC AGCTTCGTAG CTTGATGGAA 900 AGCTTACCGG GAAAGAAAGT GGGAGCAGAA GACATTGAAA AAACAATAAA GGCATGCA/U 960 CCCAGTGACC AGATCCTGAA GCTGCTCAGT TTGTGGCGAA TAAAAAATGG CGACCAAGAC 1020 ACCTTGAAGG GCCTAATGCA CGCACTAAAG CACTCAAAGA CGTACCACTT TCCCAAAACT 1080 GTCACTCAGA GTCTAAAGAA GACCATCAGG TTCCTTCACA GCTTCACAAT GTACAAATTG 1140 TATCAGAAGT TATTTHAGA AATGATAGGT AACCAGGTCC AATCACTAAA AATAACCTGC 1200 ΤΤΛΤΛΑ 1206 序列號碼：84 序列長度：1 2 Ο 6 序列型：核酸鏈數：1 經濟部中央標準局員工消費合作社印製 (請先閲讀背面之注意事項再填寫本頁) 局部解剖狀：直鏈狀序列種類：c D N A ( 0 C I F - C 2 0 S ) 序狎·· ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAArt GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 30(3 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 152 3 8 0 7 6 538049 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明（153) CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 GTTTGCAAAA GATGTCCAGA TGGGTTCTTC TCAAATGAGA CGTCATCTAA AGCACCCTGT 480 AGAAAACACA CAAATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG AAATGCAACA 540 CACGACAACA TATGTTCCGG AAACAGTGAA TCAACTCAAA AATGTGGAAT AGATGTTACC 600 CTGAGTGAGG AGGCATTCTT CAGGTTTGCT GTTCCTACAA AGTTTACGCC TAACTGGCTT 660 AGTGTCTTGG TAGACAATTT GCCTGGCACC AAAGTAAACG CAGAGAGTGT AGAGAGGATA 720 AAACGGCAAC ACAGCTCACA AGAACAGACT TTCCAGCTGC TGAAGTTATG GAAACATCAA 780 AACAAAGACC AAGATATAGT CAAGAAGATC ATCCAAGATrt TTGACCTCTG TGftAAACAGyC 840 GTGCAGCGGC ACATTGGACA TGCTAACCTC ACCTTCGAGC AGCTTCGTAG CTTGATGGAA 900 AGCTTACCGG GAAAGAAAGT GGGAGCAGAA GACATTGAAA AAACAATAAA GGCATGCAAA 960 CCC/IGTGACC AGATCCTGAA GCTGCTCAGT nGTGGCGAA T‘4A/\AAATGG CGACCAAGAC 〖020 ACCTTGAAGG GCCTAATGCA CGCACTAAAG CACTCAAAGA CGTACCACTT TCCCAAAACT 1080 GTCACTCAGA GTCTArtAGArt GACCATCAGG TTCCTTCrtCA GCTTCACAAT GTACrtAATTG 1140 TATCAGArtGT TATTTTTAGA AATGrtTAGGT AACCrtGGTCC AATCAGTAA/\ AATAAGCTGC 1200 ΤΤΑΤΛΑ 1206 序列號碼：8 5 序列長度：1206 序列型：核酸鐽數：1 局部解剖狀：直鐽狀序列種類：cDNA(0CIF-C21S) 序列： ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC [30 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 (請先閱讀背面之注意事項再填寫本頁) 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 153 38 076 538049 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明（154) CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAArt 360 CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 GTTTGCAAAA GATGTCCAGA TGGGTTCTTC TCAAATGAGA CGTCATCTAA AGCACCCTGT 480 AGAAAACACA CAAATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG AAATGCAACA 540 CACGACAACA TATGTTCCGG AAACAGTGAA TCAACTCAAA AATGTGGAAT AGATGTTACC 600 CTGTGTGAGG AGGCATTCTT CAGGTTTGCT GTTCCTACAA AGTTTACGCC TAACTGGCTT 660 AGTGTCTTGG TAGACAATTT GCCTGGCACC AAAGTAAACG CAGAGAGTGT AGAGAGGATA 720 y AAACGGCAAC ACAGCTCACA AGAACAGACT TTCCAGCTGC TGAAGTTATG GAAACATCAA 780 AACAAAGACC AAGATATAGT CAAGAAGATC ATCCAAGATA TTGACCTCAG TGAAAACAGC 840 GTGCAGCGGC ACATTGGACA TGCTAACCTC ACCTTCGAGC AGCTTCGTAG CTTGATGGAA 900 AGCTTACCGG GAAAGAAAGT GGGAGCAGAA GACATTGAAA ΑΑΑΟΛΛΤΑΑΑ GGCATGCAAA 960 CCCAGTGACC AGATCCTGAA GCTGCTCAGT TTGTGGCGArt TAAilAAi\TGG CGACCrtAGAC 1020 ACCTTGAAGG GCCTAATCCA CGCACTAAAG CACTCAAAGrt CGTACCACTT TCCCAAAACT 1080 GTCACTCAGA GTCTAAAGAA GACCATCAGG TTCCTTCACA GCTTCACArtT GTACAAATTG 1140 TATCAGAAGT TATTTTTAGA AATGATAGGT AACCAGGTCC AATCAGTAAA AATAAGCTGC 1200 ΤΤΑΤΑΛ 1206 序列號碼：86 序列長度：1 2 Ο 6 序列型：核酸鐽數：1 局部解剖狀··直鏈狀序列種_:cDNA(0CIF-C22S) 序列： ---------— (請先閱讀背面之注意事項再填寫本頁)This paper size is applicable to Chinese National Standard (CNS) A4 specification (210X 297 mm) 151 3 8 0 7 6 538049 A7 B7 V. Description of invention (152) GTTTGCAAAA GATGTCCAGA TGGGTTCTTC TCAAATGAGA CGTCATCTAA AGCACCCTGT 480 AGAAAACACA CAAATTGCAG TGTCTTTGCGCACACATG AAACAGTGAA TCAACTCAAA AftAGTGGAAT AGATGTTACC 600 CTGTGTGAGG AGGCATTCTT CAGGTTTGCT GTTCCTACAA AGTTTACGCC TAACTGGCTT 660 AGTGTCTTGG TAGACAATTT GCCTGGCACC AAAGTAAACG CAGAGAGTGT AGAGAGGATA 720 AAACGGCAAC ACAGCTCACA AGAACAGACT TTCCAGCTGC TGAAGTTATG GAAACATCAA 780 AACAAAGACC AAGATATAGT CAAGAAGATC ATCCAAGATA TTGACCTCTG TGAAAACAGC 840 GTGCAGCGGC ACATTGGACA TGCTAACCTC ACCTTCGAGC AGCTTCGTAG CTTGATGGAA 900 AGCTTACCGG GAAAGAAAGT GGGAGCAGAA GACATTGAAA AAACAATAAA GGCATGCA / U 960 CCCAGTGACC AGATCCTGAA GCTGCTCAGT TTGTGGCGAA TAAAAAATGG CGACCAAGAC 1020 ACCTTGAAGG GCCTAATGCA CGCACTAAAG CACTCAAAGA CGTACCACTT TCCCAAAACT 1080 GTCACTCAGA GTCTAAAGAA GACCATCAGG TTCCTTCACA GCTTCAAT GTACAAGAGA T140TACAAG TAGGT AACCAGGTCC AATCACTAAA AATAACCTGC 1200 ΤΤΛΤΛΑ 1206 Sequence number: 84 Sequence length: 1 2 〇 6 Sequence type: Number of nucleic acid chains: 1 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling this page) Partial anatomical shape: linear sequence type: c DNA (0 CIF - C 2 0 S) sequence sex ·· ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAArt GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 30 (3 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 This paper is in accordance with the Chinese National Standard (CNS) A4 specification (210X 3 049 0509) 6 standard of the Ministry of Economic Affairs 6 520 mm Printed by the cooperative A7 B7 V. Description of the invention (153) CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 GTTTGC AAAA GATGTCCAGA TGGGTTCTTC TCAAATGAGA CGTCATCTAA AGCACCCTGT 480 AGAAAACACA CAAATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG AAATGCAACA 540 CACGACAACA TATGTTCCGG AAACAGTGAA TCAACTCAAA AATGTGGAAT AGATGTTACC 600 CTGAGTGAGG AGGCATTCTT CAGGTTTGCT GTTCCTACAA AGTTTACGCC TAACTGGCTT 660 AGTGTCTTGG TAGACAATTT GCCTGGCACC AAAGTAAACG CAGAGAGTGT AGAGAGGATA 720 AAACGGCAAC ACAGCTCACA AGAACAGACT TTCCAGCTGC TGAAGTTATG GAAACATCAA 780 AACAAAGACC AAGATATAGT CAAGAAGATC ATCCAAGATrt TTGACCTCTG TGftAAACAGyC 840 GTGCAGCGGC ACATTGGACA TGCTAACCTC ACCTTCGAGC AGCTTCGTAG CTTGATGGAA 900 AGCTTACCGG GAAAGAAAGT GGGAGCAGAA GACATTGAAA AAACAATAAA GGCATGCAAA 960 CCC / IGTGACC AGATCCTGAA GCTGCTCAGT nGTGGCGAA T'4A / \ AAATGG CGACCAAGAC 〖020 ACCTTGAAGG GCCTAATGCA CGCACTAAAG CACTCAAAGA CGTACCACTT TCCCAAAACT 1080 GTCACTCAGA GTCTArtAGArt GACCATCAGG TTCCTTCrtCA GCTTCACAAT GTACrtAATTG 1140 TATCAGArtGT TATTTTTAGA AATGrtTAGGT AACCrtGGTCC AATCAGTAA / \ AATAAGCTGC 1200 ΤΤΑΤΛΑ 1206 Sequence number: 8 5 Sequence length: 1206 Sequence type: Nucleic acid Da: 1 topographical shape: straight Da-like sequence type: cDNA (0CIF-C21S) sequence: ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC [30 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 (Please read the precautions on the back before filling this page) This paper size applies Chinese National Standard (CNS) A4 (210X297 mm) 153 38 076 538049 A7 B7 printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs instructions (154) CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAArt 360 CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 GTTTGCAAAA GATGTCCAGA TGGGTTCTTC TCAAATGAGA CGTCATCTAA AGCACCCTGT 480 AGAAAACACA CAAATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG AAATGCAACA 540 CACGACAACA TATGTTCCGG AAACAGTGAA TCAACTCAAA AATGTGGAAT AGATG TTACC 600 CTGTGTGAGG AGGCATTCTT CAGGTTTGCT GTTCCTACAA AGTTTACGCC TAACTGGCTT 660 AGTGTCTTGG TAGACAATTT GCCTGGCACC AAAGTAAACG CAGAGAGTGT AGAGAGGATA 720 y AAACGGCAAC ACAGCTCACA AGAACAGACT TTCCAGCTGC TGAAGTTATG GAAACATCAA 780 AACAAAGACC AAGATATAGT CAAGAAGATC ATCCAAGATA TTGACCTCAG TGAAAACAGC 840 GTGCAGCGGC ACATTGGACA TGCTAACCTC ACCTTCGAGC AGCTTCGTAG CTTGATGGAA 900 AGCTTACCGG GAAAGAAAGT GGGAGCAGAA GACATTGAAA ΑΑΑΟΛΛΤΑΑΑ GGCATGCAAA 960 CCCAGTGACC AGATCCTGAA GCTGCTCAGT TTGTGGCGArt TAAilAAi \ TGG CGACCrtAGAC 1020 ACCTTGAAGG GCCTAATCCA CGCACTAAAG CACTCAAAGrt CGTACCACTT TCCCAAAACT 1080 GTCACTCAGA GTCTAAAGAA GACCATCAGG TTCCTTCACA GCTTCACArtT GTACAAATTG 1 ACC sequence: 1 sequence number: 1 · Straight-chain sequence species_: cDNA (0CIF-C22S) Sequence: ---------— (Please read the precautions on the back before filling in this page)

、1T 4 本紙張尺度適用中國國家標準（CNS ) Α4規格（21〇X297公釐） 154 3 8 0 7 6 538049 A7 B7 經濟部中央標準局.員工消費合作社印製五、發明説明（1 5 5) 1 I ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 1 1 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 1 I TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 1 1 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 請先閱讀 1 I CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 1 1 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 背面 1 | CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 之注意 1 I GTTTGCAAAA GATGTCCAGA TGGGTTCTTC TCAAATGAGA CGTCATCTAA AGCACCCTGT 480 事項 1 1 AGAAAACACA CAAATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG AAATGCAACA 540 再填寫 I 1 CACGACAACA TATGTTCCCG AAACAGTGAA TCAACTCAAA AATGTGGAAT AGATGTTACC / 600 本頁 CTGTGTGAGG AGGCATTCTT CAGGTTTGCT GTTCCTACAA AGTTTACGCC TAACTGGCn 660 1 I AGTGTCTTGG TAGACAATTT GCCTGGCACC AAAGTAAACG CAGAGAGTGT AGAGAGGATA 720 1 1 AAACGGCAAC ACAGCTCACA AGAACAGACT TTCCAGCTGC TGAAGTTATG GAAACATCAA 780 1 | AACAAAGACC AAGATATAGT CAAGAAGATC ATCCAAGATA TTGACCTCTG TGrtAAACAGC 340 訂 GTGCAGCGGC ACATTGGACA TGCTrtACCTC ACCTTCGrtGC AGCTTCGTrtG CTTGATGGAA 900 1 1 AGCTTACCCG GAAAGAAAGT GGGAGCAGAA GACATTGAAA AAACAATAAA GGCAAGCAAA 960 1 1 CCCAGTGACC AGATCCTGAA GCTGCTCAGT TTGTGGCGAA TAAAAAATGG CGACCAAGAC 1020 1 1 ACCTTGAAGG GCCTAATGCA CGCACTAAAG CACTCAAAGA CGTACCACTT TCCCAAAACT 1080 4 1 GTCACTCAGA GTCTAAAGAA GACCATCAGG TTCCTTCACA GCTTCACAAT GTACAAATTG 1140 TATCAGArtGT TATTTTTAGA AATGATAGGT AACCAGGTCC AATCAGTAAA AATAAGCTGC 1200 1 | TTATAA 1206 1 1 序列號碼：87 1 1 序列長度：1206 1 1 序列型：核酸 1 1 鏈數：1 1 1 局部解剖狀··直鏈狀 1 I 序列種類：c D N A ( 0 C I F - C 2 3 S ) 1 1 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） ^ 5 5 38 0 76 538049 A7 B7 經濟部中央標準局員工消費合作社印製五、發明説明（l56) 序列： ATGAACAACT TGCTGTGCTG CGCGCTCGTG CAGGAAACGT TTCCTCCAAA GTACCTTCAT TGTGACAAAT GTCCTCCTGG TACCTACCTA GTGTGCGCCC CTTGCCCTGA CCACTACTAC CTATACTGCA GCCCCGTGTG CAAGGAGCTG CACAACCGCG TGTGCGAATG CAAGGAAGGG CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTTTGCAAAA GATGTCCAGA TGGGTTCTTC AGAAAACACA CAAATTGCAG TGTCTTTGGT CACGACAACA TATGTTCCGG AAACAGTGAA CTGTGTGAGG AGGCATTCTT CAGGTTTGCT AGTGTCTTGG TAGACAATTT GCCTGGCACC A^ACGGCAAC ACAGCTCACA AGAACAGACT .CAAAGACC ΑΛϋΑΤΑΤΑΓ/Γ CAAGAAGATC GTGCAGCGGC ACATTGGACA TGCTAACCTC AGCTTACCGG GAAAGAAAGT GGGAGCAGAA CCCAGTGACC AGATCCTGAA GCTGCTCAGT ACCTTGAAGG GCCTAATGCA CGCACTAAAG GTCACTCAGA GTCTAAAGAA GACCATCAGG TATCAGAf\GT TATTTTTAGA AATGATAGGT TTATAA 序列號碼：88 序列長度：1 0 8 3 序列型：核酸鏈數：1 局部解剖狀：直鏈狀、 1T 4 This paper size is applicable to China National Standard (CNS) A4 specification (21 × 297 mm) 154 3 8 0 7 6 538049 A7 B7 Printed by the Central Standards Bureau of the Ministry of Economic Affairs. Printed by the Consumer Consumption Cooperative (1 5 5 ) 1 I ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 1 1 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 1 I TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 1 1 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 read 1 I CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 1 1 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 back 1 | CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 of Note 1 I GTTTGCAAAA GATGTCCAGA TGGGTTCTTC TCAAATGAGA CGTCATCTAA AGCACCCTGT 480 items 1 1 AGAAAACACA CAAATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG AAATGCAACA 540 to fill out I 1 CACGACAACA TATGTTCCCG AAACAGTGAA TCAACTCAAA AATGTGGAAT AGATGT TACC / 600 page CTGTGTGAGG AGGCATTCTT CAGGTTTGCT GTTCCTACAA AGTTTACGCC TAACTGGCn 660 1 I AGTGTCTTGG TAGACAATTT GCCTGGCACC AAAGTAAACG CAGAGAGTGT AGAGAGGATA 720 1 1 AAACGGCAAC ACAGCTCACA AGAACAGACT TTCCAGCTGC TGAAGTTATG GAAACATCAA 780 1 | AACAAAGACC AAGATATAGT CAAGAAGATC ATCCAAGATA TTGACCTCTG TGrtAAACAGC 340 custom GTGCAGCGGC ACATTGGACA TGCTrtACCTC ACCTTCGrtGC AGCTTCGTrtG CTTGATGGAA 900 1 1 AGCTTACCCG GAAAGAAAGT GGGAGCAGAA GACATTGAAA AAACAATAAA GGCAAGCAAA 960 1 1 CCCAGTGACC AGATCCTGAA GCTGCTCAGT TTGTGGCGAA TAAAAAATGG CGACCAAGAC 1020 1 1 ACCTTGAAGG GCCTAATGCA CGCACTAAAG CACTCAAAGA CGTACCACTT TCCCAAAACT 1080 4 1 GTCACTCAGA GTCTAAAGAA GACCATCAGG TTCCTTCACA GCTTCACAAT GTACAAATTG 1140 TATCAGArtGT TATTTTTAGA AATGATAGGT AACCAGGTCC AATCAGTAAA AATAAGCTGC 1200 1 | TTATAA 1206 1 1 sequence number: 87 1 1 Sequence length: 1206 1 1 Sequence type: Nucleic acid 1 1 Number of strands: 1 1 1 Local anatomy · linear 1 I Sequence type: c DNA (0 CIF-C 2 3 S) 1 1 This paper size applies the Chinese National Standard (CNS) A4 specification (210X 297 mm) ^ 5 5 38 0 76 538049 A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (l56) Sequence: ATGAACAACT TGCTGTGCTG CGCGCTCGTG CAGGAAACGT TTCCTCCAAA GTACCTTCAT TGTGACAAAT GTCCTCCTGG TACCTACCTA GTGTGCGCCC CTTGCCCTGA CCACTACTAC CTATACTGCA GCCCCGTGTG CAAGGAGCTG CACAACCGCG TGTGCGAATG CAAGGAAGGG CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTTTGCAAAA GATGTCCAGA TGGGTTCTTC AGAAAACACA CAAATTGCAG TGTCTTTGGT CACGACAACA TATGTTCCGG AAACAGTGAA CTGTGTGAGG AGGCATTCTT CAGGTTTGCT AGTGTCTTGG TAGACAATTT GCCTGGCACC A ^ ACGGCAAC ACAGCTCACA AGAACAGACT .CAAAGACC ΑΛϋΑΤΑΤΑΓ / Γ CAAGAAGATC GTGCAGCGGC ACATTGGACA TGCTAACCTC AGCTTACCGG GAAAGAAAGT GGGAGCAGAA CCCAGTGACC AGATCCTGAA GCTGCTCAGT ACCTTGAAGG GCCTAATGCA CGCACTAAAG GTCACTCAGA GTCTAAAGAA GACCATCAGG TATCAGAf \ GT TATTTTTAGA AATGATAGGT TTATAA sequence number: 88 sequence length: 1 linear strand type: 1 0 8 3 sequence:

TTTCTGGACA TATGACGAAG AAACAACACT ACAGACAGCT CAGTACGTCA CGCTACCTTG GTGCAAGCTG TCAAATGAGA CTCCTGCTAA TCAACTCAAA GTTCCTACArt AAAGTArtACG TTCCAGCTGC ATCCAAGATA ACCTTCGAGC GACATTGAAA TTGTGGCGAA CACTCAAAGA TTCCTTCACA AACCAGGTCCTTTCTGGACA TATGACGAAG AAACAACACT ACAGACAGCT CAGTACGTCA CGCTACCTTG GTGCAAGCTG TCAAATGAGA CTCCTGCTAA TCAACTCAAA GTTCCTACArt AAAGTArtACG TTCCAGCTGC ATCCAAGATA ACCTTCGAGA GACATTGAAA TTGTGGCGAA CACTCCAAAA TT

TCTCCATTAA AAACCTCTCA GTACAGCAAA GGCACACCAG AGCAGGAGTG AGATAGAGTT GAACCCCAGA CGTCATCTAA CTCAGAAAGG AATGTGGAAT AGTTTACGCC CAGAGAGTGT TGAAGTTATG TTGACCTCTG AGCTTCGTAG AAACAATAAA TAAAAAATGG CGTACCACn GCTTCACAAT AAT*CAGTAAA GTGGACCACC 60 TCAGCTGTTG 120 GTGGAAGACC 180 TGACGAGTGT 240 CAATCGCACC 300 CTGCTTGAAA 360 GCGAAATACA 420 AGCACCCTGT 480 t AAATGCAACA 540 AGATGTTACC 600 TAACTGGCTT 660 AGAGAGGATA 720 GAAACATCAA 780 TGAAAACAGC 840 CTTGATGGAA ')0 GGCATGCAAA 960 CGACCAAGAC 1020 TCCCAAAACT 1080 GTACAAATTG 1140 AATAAGCAGC 1200 1206 (請先閱讀背面之注意事項再填寫本頁) 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 156 3 8 0 7 6 538049 A7 B7 五、發明説明（157) 序列種類·· cDNA(OCIF-DCRl) (請先閱讀背面之注意事項再填寫本頁) 經濟部中央標準局員工消費合作社印製序列：TCTCCATTAA AAACCTCTCA GTACAGCAAA GGCACACCAG AGCAGGAGTG AGATAGAGTT GAACCCCAGA CGTCATCTAA CTCAGAAAGG AATGTGGAAT AGTTTACGCC CAGAGAGTGT TGAAGTTATG TTGACCTCTG AGCTTCGTAG AAACAATAAA TAAAAAATGG CGTACCACn GCTTCACAAT AAT * CAGTAAA GTGGACCACC 60 TCAGCTGTTG 120 GTGGAAGACC 180 TGACGAGTGT 240 CAATCGCACC 300 CTGCTTGAAA 360 GCGAAATACA 420 AGCACCCTGT 480 t AAATGCAACA 540 AGATGTTACC 600 TAACTGGCTT 660 AGAGAGGATA 720 GAAACATCAA 780 TGAAAACAGC 840 CTTGATGGAA ') 0 GGCATGCAAA 960 CGACCAAGAC 1020 TCCCAAAACT 1080 GTACAAATTG 1140 AATAAGCAGC 1200 1206 (Please read the precautions on the back before filling out this page) This paper size applies the Chinese National Standard (CNS) A4 specification (210X 297 mm) 156 3 8 0 7 6 538049 A7 B7 V. Description of the invention (157) Sequence type · cDNA (OCIF-DCRl) (Please read the notes on the back before filling out this page) The sequence printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs:

ATGAACAACTATGAACAACT

CAGGAACCTTCAGGAACCTT

TACTGCAGCCTACTGCAGCC

AACCGCGTGTAACCGCGTGT

AGGAGCTGCCAGGAGCTGCC

TGCAAAAGATTGCAAAAGAT

AAACACACAAAAACACACAA

GACAACATATGACAACATAT

TGTGAGGAGGTGTGAGGAGG

GTCTTGGTAGGTCTTGGTAG

CGGCAACACACGGCAACACA

AAAGACCAAGAAAGACCAAG

CAGCGGCACACAGCGGCACA

TTACCGGGAATTACCGGGAA

AGTGACCAGAAGTGACCAGA

TTGAAGGGCCTTGAAGGGCC

ACTCAGAGTCACTCAGAGTC

CAGAAGTTATCAGAAGTTAT

TAATAA

TGCTGTGCTGTGCTGTGCTG

GCCCTGACCAGCCCTGACCA

CCGTGTGCAACCGTGTGCAA

GCGAATGCAAGCGAATGCAA

CTCCTGGATTCTCCTGGATT

GTCCAGATGGGTCCAGATGG

ATTGCAGTGTATTGCAGTGT

GTTCCGGAAAGTTCCGGAAA

CATTCTTCAGCATTCTTCAG

ACAATTTGCCACAATTTGCC

GCTCACAAGAGCTCACAAGA

ATATAGTCAAATATAGTCAA

TTGGACATGCTTGGACATGC

AGAAAGTGGGAGAAAGTGGG

TCCTGAAGCTTCCTGAAGCT

TAATGCACGCTAATGCACGC

TAAAGAAGACTAAAGAAGAC

TTTTAGAAATTTTTAGAAAT

CGCGCTCGTGCGCGCTCGTG

CTACTACACACTACTACACA

GGAGCTGCAGGGAGCTGCAG

GGAAGGGCGCGGAAGGGCGC

TGGAGTGGTGTGGAGTGGTG

GTTCTTCTCAGTTCTTCTCA

CTTTGGTCTCCTTTGGTCTC

CAGTGAATCACAGTGAATCA

GTTTGCTGTTGTTTGCTGTT

TGGCACCAAATGGCACCAAA

ACAGACTTTCACAGACTTTC

GAAGATCATCGAAGATCATC

TAACCTCACCTAACCTCACC

AGCAGAAGACAGCAGAAGAC

GCTCAGTTTGGCTCAGTTTG

ACTAAAGCACACTAAAGCAC

CATCAGGTTCCATCAGGTTC

GATAGGTAACGATAGGTAAC

TTTCTGGACATTTCTGGACA

GACAGCTGGCGACAGCTGGC

TACGTCAAGCTACGTCAAGC

TACCTTGAGATACCTTGAGA

CAAGCTGGAACAAGCTGGAA

AATGAGACGTAATGAGACGT

CTGCTAACTCCTGCTAACTC

ACTCAAAAATACTCAAAAAT

CCTACAAAGTCCTACAAAGT

GTAAACGCAGGTAAACGCAG

CAGCTGCTGACAGCTGCTGA

CAAGATATTGCAAGATATTG

TTCGAGCAGCTTCGAGCAGC

ATTGAAAAAAATTGAAAAAA

TGGCGAATAATGGCGAATAA

TCAAAGACGTTCAAAGACGT

CTTCACAGCTCTTCACAGCT

CAGGTCCAATCAGGTCCAAT

TCTCCATTAATCTCCATTAA

ACACCAGTGAACACCAGTGA

AGGAGTGCAAAGGAGTGCAA

TAGAGTTCTGTAGAGTTCTG

CCCCAGAGCGCCCCAGAGCG

CATCTAAAGCCATCTAAAGC

AGAAAGGAAAAGAAAGGAAA

GTGGAATAGAGTGGAATAGA

TTACGCCTAATTACGCCTAA

AGAGTGTAGAAGAGTGTAGA

AGTTATGGAAAGTTATGGAA

ACCTCTGTGAACCTCTGTGA

TTCGTAGCTTTTCGTAGCTT

CAATAAAGGCCAATAAAGGC

AAAATGGCGAAAAATGGCGA

ACCACTTTCCACCACTTTCC

TCACAATGTATCACAATGTA

CAGTAAAAAT 序列號碼：89 序列長度：1 〇 8 Ο 序列型：核酸鏈數：1 局部解剖狀：直鏈狀序列種類·· c D N A ( 0 C I F - D C R 2 ) GTGGACCACC 60 CGAGTGTCTA 120 TCGCACCCAC 180 CTTGAAACAT 240 AAATACAGTT 300 ACCCTGTAGA 360 / TGCAACACAC 420 TGTTACCCTG 480 CTGGCTTAGT 540 GAGGATA/\AA 600 ACATCArtAAC 660 AAACAGCGTG 720 GATGGArtAGC 780 ATGCAAACCC 840 CCAAGACACC 900 CftrtAACTGTC 960 CrtrtATTGTAT 1020 AAGCTGCTTA 1080 1083 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 157 3 8 0 7 6 538049 A7 B7 五、發明説明（1 58) 序列：CAGTAAAAAT Sequence number: 89 Sequence length: 1 〇8 〇 Sequence type: Nucleic acid strand number: 1 Topographic anatomy: Linear sequence type · c DNA (0 CIF-DCR 2) GTGGACCACC 60 CGAGTGTCTA 120 TCGCACCCAC 180 CTTGAAACAT 240 AAATACAGTT 300 ACCCTGTAGA 360 / TGCAACACAC 420 TGTTACCCTG 480 CTGGCTTAGT 540 GAGGATA / \ AA 600 ACATCArtAAC 660 AAACAGCGTG 720 GATGGArtAGC 780 ATGCAAACCC 840 CCAAGACACC 900 CftrtAACTGTC 960 CrtrtATTGTAT 1020 AAGCTGCT standard (According to China) 8 0 7 6 538049 A7 B7 V. Description of the invention (1 58) Sequence:

ATGAACAACTATGAACAACT

CAGGAAACGTCAGGAAACGT

TGTGACAAATTGTGACAAAT

GTGTGCGCCGGTGTGCGCCG

AGCTGCCCTCAGCTGCCCTC

AAAAGATGTCAAAAGATGTC

CACACAAATTCACACAAATT

AACATATGTTAACATATGTT

GAGGAGGCATGAGGAGGCAT

TTGGTAGACATTGGTAGACA

CAACACAGCTCAACACAGCT

GACCAACATAGACCAACATA

CGGCACATTGCGGCACATTG

CCGdGAAAGACCGdGAAAGA

GACCAGATCCGACCAGATCC

AAGGGCCTAAAAGGGCCTAA

CAGAGTCTAACAGAGTCTAA

AAGTTATTTTAAGTTATTTT

TGCTGTGCTGTGCTGTGCTG

TTCCTCCAAATTCCTCCAAA

GTCCTCCTGGGTCCTCCTGG

AATGCAAGGAAATGCAAGGA

CTGGATTTGGCTGGATTTGG

CAGATGGGTTCAGATGGGTT

GCAGTGTCTTGCAGTGTCTT

CCGGAAACAGCCGGAAACAG

TCTTCAGGTTTCTTCAGGTT

ATTTGCCTGGATTTGCCTGG

CACAAGAACACACAAGAACA

TAGTCAAGrtATAGTCAAGrtA

GACATGCTAAGACATGCTAA

AAGTGGGAGCAAGTGGGAGC

TGAAGCTGCTTGAAGCTGCT

TGCACGCACTTGCACGCACT

AGAAGACCATAGAAGACCAT

TAGAAATGATTAGAAATGAT

CGCGCTCGTGCGCGCTCGTG

GTACCTTCATGTACCTTCAT

TACCTACCTATACCTACCTA

AGGGCGCTACAGGGCGCTAC

AGTGGTGCAAAGTGGTGCAA

CTTCTCAAATCTTCTCAAAT

TGGTCTCCTGTGGTCTCCTG

TGAATCAACTTGAATCAACT

TGCTGTTCCTTGCTGTTCCT

CACCAAAGTACACCAAAGTA

GACmCCAG GATCATCCArtGACmCCAG GATCATCCArt

CCTCACCTTCCCTCACCTTC

AGAAGACATTAGAAGACATT

CAGTTTGTGG AAAGCACTCrtCAGTTTGTGG AAAGCACTCrt

CAGGTTCCHCAGGTTCCH

AGGTAACCAGAGGTAACCAG

TTTCTGGACATTTCTGGACA

TATGACGAAGTATGACGAAG

AAACAACACTAAACAACACT

CTTGAGATAGCTTGAGATAG

GCTGGAACCCGCTGGAACCC

GAGACGTCATGAGACGTCAT

CTAACTCAGACTAACTCAGA

CAAAAATGTGCAAAAATGTG

ACAAAGTTTAACAAAGTTTA

AACGCAGAGAAACGCAGAGA

CTGCTGAAGTCTGCTGAAGT

GATrtTTGACCGATrtTTGACC

GAGCAGCTTCGAGCAGCTTC

GAAArtAACAAGAAArtAACAA

CGAATAAAAACGAATAAAAA

AAGACGTACCAAGACGTACC

CACAGCTTCACACAGCTTCA

GTCCAATCAGGTCCAATCAG

TCTCCATTAATCTCCATTAA

AAACCTCTCAAAACCTCTCA

GTaCAGCAAAGTaCAGCAAA

AGTTCTGCTTAGTTCTGCTT

CAGAGCGAAACAGAGCGAAA

CTAAAGCACCCTAAAGCACC

AAGGAAATGCAAGGAAATGC

GAATAGATGTGAATAGATGT

CGCCTAACTGCGCCTAACTG

GTCTAGAGAGGTCTAGAGAG

TATGGAAACATATGGAAACA

TCTGTGAAAATCTGTGAAAA

GTAGCTTGATGTAGCTTGAT

TAAAGGCATGTAAAGGCATG

ATGGCGACCAATGGCGACCA

ACTTTCCCAAACTTTCCCAA

CAATGTACAACAATGTACAA

TAAAAATAAG GTGGACCACC 60 TCAGCTGTTG 120 GTGGAAGACC 180 GAAACATAGG 240 TACAGTTTGC 300 CTGTAGAArtA 360 t AACACACGAC 420 TACCCTGTGT 480 GCTTAGTGTC 540 GATA;\AACGG 600 TCrtAAACAAA 660 CAGCGTGCAG 720 GGAAAGCTTA 780 CAAACCCAGT 840 AGACACCTTG 900 AAGTGTCACT 960 ATTGTATCAG 1020 CTGCTTATAA 1080 (請先閱讀背面之注意事項再填寫本頁) 經濟部中央標準局員工消費合作社印製序列號碼：90 序列長度：1 0 9 2 序列型：核酸鐽數：1 局部解剖狀：直鏈狀序列種類：cDNA(0CIF-DCR3) 序列：本紙張尺度適用中國國家標準（CNS ) A4規格（2丨〇X297公釐） 158 3 8 07 6 經濟部中央標準局員工消費合作社印製 538049 A7 B7 五、發明説明（159) ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCAGATG TCCAGATGGG TTCTTCTCAA ATGAGACGTC ATCTAAAGCA 360 CCCTGTAGAA AACACACAAA TTGCAGTGTC TTTGGTCTCC TGCTAACTCA GAAAGGAAAT 420 GCAACACACG ACAACATATG TTCCGGAAAC AGTGAATCAA CTCAAAAATG TGGAATAGAT 480 GTTACCCTGT GTGAGGAGGC ATTCTTCAGG TTTGCTGTTC CTACAAAGTT TACGCCTAAC 540 TGGCTTAGTG TCTTGGTAGA CAATTTGCCT GGCACCAAAG TAAACGCAGA GAGTGTAGAG 600 AGGATAAAAC GGCAACACAG CTCACAAGAA CAGrtCTTTCC AGCTGCTGAA GTTATGGAAA 660 CATCAAAACA AAGACCAAGA TATAGTCAAG AAGATC/VrCC AAGrtTATTGA CCTCTGTGArt 720 AACAGCGTGC AGCGGCACAT TGGACATGCT AACCTCACCT TCGAGCAGCT TCGTAGCTTG 780 ATGGAAAGCT TACCGGGAAA GAAAGTGGGA GCAGAAGACA TTGAAAAAAC AATAAAGGCA 840 TGCA'AACCCA GTGACCAGAT CCTGAAGCTG CTCAGTTTGT GGCGAATArtA AAATGGCGAC 900 CAAGACACCT TGAAGGGCCT AATGCACGCA CTAAAGCACT CAAAGACGTA CCACTTTCCC 960 AAAACTGTCA CTCAGAGTCT AAAGAAGACC ATCAGGTTCC TTCACAGCTT CACAATGTAC 1020 AAATTGTATC AGAAGTTATT TTTAGAAATG ATAGGTAACC AGGTCCAATC AGTAAAAATA 1080 AGCTGCTTAT AA 1092 序列號碼：9 1 序列長度：1 Ο 8 Ο 序列型：核酸鏈數：1 局部解剖狀：直鏈狀序列種類：cDNA(OCIF-DCR4) 序列： (請先閱讀背面之注意事項再填寫本頁)TAAAAATAAG GTGGACCACC 60 TCAGCTGTTG 120 GTGGAAGACC 180 GAAACATAGG 240 TACAGTTTGC 300 CTGTAGAArtA 360 t AACACACGAC 420 TACCCTGTGT 480 GCTTAGTGTC 540 GATA; \ AACGG 600 TCrtAAACTA TCAC 780ATCAC 780 CATGGTAGAG (Fill in this page) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs Serial Number: 90 Sequence Length: 1 0 9 2 Sequence Type: Nucleic Acid Number: 1 Local Anatomy: Linear Sequence Type: cDNA (0CIF-DCR3) Sequence ： This paper size applies to China National Standard (CNS) A4 specification (2 丨〇297297 mm) 158 3 8 07 6 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 538049 A7 B7 V. Description of the invention (159) ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCTCT GGCAC GCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCAGATG TCCAGATGGG TTCTTCTCAA ATGAGACGTC ATCTAAAGCA 360 CCCTGTAGAA AACACACAAA TTGCAGTGTC TTTGGTCTCC TGCTAACTCA GAAAGGAAAT 420 GCAACACACG ACAACATATG TTCCGGAAAC AGTGAATCAA CTCAAAAATG TGGAATAGAT 480 GTTACCCTGT GTGAGGAGGC ATTCTTCAGG TTTGCTGTTC CTACAAAGTT TACGCCTAAC 540 TGGCTTAGTG TCTTGGTAGA CAATTTGCCT GGCACCAAAG TAAACGCAGA GAGTGTAGAG 600 AGGATAAAAC GGCAACACAG CTCACAAGAA CAGrtCTTTCC AGCTGCTGAA GTTATGGAAA 660 CATCAAAACA AAGACCAAGA TATAGTCAAG AAGATC / VrCC AAGrtTATTGA CCTCTGTGArt 720 AACAGCGTGC AGCGGCACAT TGGACATGCT AACCTCACCT TCGAGCAGCT TCGTAGCTTG 780 ATGGAAAGCT TACCGGGAAA GAAAGTGGGA GCAGAAGACA TTGAAAAAAC AATAAAGGCA 840 TGCA'AACCCA GTGACCAGAT CCTGAAGCTG CTCAGTTTGT GGCGAATArtA AAATGGCGAC 900 CAAGACACCT TGAAGGGCCT AATGCACGCA CTAAAGCACT CAAAGACGTA CCACTTTCCC 960 AAAACTGTCA CTCAGAGTCT AAAGAAGACC ATCAGGTTCC TTCACAGCTT CACAATGTAC 1020 AAATTGTATC AGAAGTTATT TTTAGAAATG ATAGGTAACC AGGTCCAATC AGTAAAAATA 1080 AGCTGCTTAT AA 1092 Sequence number: 9 1 Sequence length: 1 Ο 8 Ο Sequence type: Nucleic acid strand number: 1 Local anatomy: Linear sequence Type: cDNA (OCIF-DCR4) Sequence: (Please read the precautions on the back before filling this page )

1T 4 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 159 3 8 0 7 6 538049 A7 B7 五、發明説明（160) ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 / GTTTGCAAAT CCGGAAACAG TGAATCAACT CAAAAATGTG GAATAGATGT TACCCTCTGT 480 GAGGAGGCAT TCTTCAGGTT TGCTGTTCCT ACAAAGTTTA CGCCTAACTG GCTTAGTGTC 540 TTGGTAGACA ATTTGCCTGG CACCAAAGTA AACGCAGAGA GTGTAGAGAG GATAAAACGG 600 CAACACAGCT CACAAGAACA GACTTTCCAG CTGCTGAAGT TATGGAAACrt TCAAAACAAA 660 GACCAAGATA TAGTCAAGAA GATCATCCAA GATAHGACC TCTGTGAAAA CAGCGTGCAG 720 CGGCACATTC GACATGCTAA CCTCACCTTC GAGCAGCTTC GTAGCTTGAT GGAAAGCTTA 780 CCGGGAAAGA AAGTGGGAGC AGAAGACATT GAAAAAACAA TAAAGGCATG CAAACCCAGT 840 GACCAGATCC TGAAGCTGCT CAGTTTGTGG CGAATAAAAA ATGGCGACCA AGACACCTTG 900 AAGGGCCTAA TGCACGCACT AAAGCACTCA AAGACGTACC ACTTTCCCAA AACTGTCACT 960 CAGAGTCTAA AGAAGACCAT CAGGTTCCTT CACAGCTTCA CAATGTACAA ATTGTATCAG 1020 AAGTTATTTT TAGAAATGAT AGGTAACCAG GTCCAATCAG TAAAAATAAG CTGCTTrtTAA 1080 經濟部中央標準局員工消費合作杜印製 (請先閱讀背面之注意事項再填寫本頁) 序列號碼：9 2 序列長度：981 序列型：核酸鏈數：1 局部解剖狀：直鏈狀序列種類：cDNA(OCIF-DDDl) 序列：本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 160 38 076 經濟部中央標準局員工消費合作社印製 538049 A7 B7 五、發明説明（1 61) ATGAACAACT TGCTGTGCTG CGCGCTCCTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 GTTTGCAAAA GATGTCCAGA TGGGTTCTTC TCAAATGAGA CGTCATCTAA AGCACCCTGT 480 / AGAAAACACA CAAATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG AAATGCAACA 540 CACGACAACA TATGTTCCGG AAACAGTGAA TCAACTCAAA AATGTGGAAT AGATrtTTGAC 600 CTCTGTGAAA ACAGCGTGCA GCGGCACATT GGACATGCTA ACCTCACCTT CGAGCAGCTT 660 CGTAGCTTGA TGGAAAGCTT ACCGGGAAAG AAAGTGGGAG CAGAAGACAT TGAAAAAACA 720 ATAAAGGCAT GCAAACCCAG TGACCAGATC CTGAAGCTGC TCAGTTTGTG GCGAATrtAAA 730 AATGGCGACC AAGACACCTT GAAGGGCCTA ATGCACGCAC TAAAGCACTC AAAGACGTAC 840 CACTTTCCCA AAACTGTCAC TCAGAGTCTA AAGAAGrtCCA TCAGGTTCCT TCACAGCTTC 900 ACAATGTACA rtATTGTATCA GAAGTTATTT TTAGrtAATGA TAGGTAACCA GGTCCAATCA 960 GTAAAAATAA GCTGCTTATA A 981 序列號碼：93 序列長度：984 序列型：核酸鏈數：1 局部解剖狀：直鏈狀序列種類·· c D N A ( 0 C I F - D D D 2 ) 序列：本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐）. ^ 3 8 0 7 6 I----------- (請先閱讀背面之注意事項再填寫本頁) 訂 4 538049 A7 B7 五、發明説明（I62) ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 CATAGGAGCT GCCCTCCTGG ATTTGGAGTG'GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 GTTTGCAAAA GATGTCCAGA TGGGTTCTTC TCAAATGAGA CGTCATCTAA AGCACCCTGT 480 AGAAAACACA CAAATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG AAATGCAACA 540 CACGACAACA TATGTTCCGG AAACAGTGAA TCAACTCAAA AATGTGGAAT AGATGTTACC 600 i CTGTGTGAGG AGGCATTCTT CAGGTTTGCT GTTCCTACAA AGTTTACGCC TAACTGGCTT 660 AGTGTCTTGG TAGACAATTT GCCTGGCACC AAAGTAAACG CAGAGAGTGT AGAGAGGATA 720 AAACGGCAAC ACAGCTCACrt AGAACAGACT TTCCAGCTGC TGAAGTTATG GAAACATCAA 780 AACAAAGACC AAGATATAGT CAAGrtAGATC ATCCAAGACG CACTAAAGCA CTCArtftGACG 840 TACCACTTTC CCAAAACTGT CACTCAGAGT CTAAAGAAGA CCATCAGGTT CCTTCACAGC 900 TTCACAATGT ACAAATTGTA TCAGAAGTTA TTTTTAGAAA TGATAGGTAA CCrtGGTCCAA 960 TCAGTAAAAA TAAGCTGCTT ATAA 984 序列號碼：94 序列長度·· 1 2 Ο Ο 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) 序列型：核酸鏈數：1 局部解剖狀：直鏈狀序列種類：cDNA(OCIF-CL) 序列：本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 162 3 8 0 7 6 538049 A7 B7 經濟部中央標準局員工消費合作社印製五、發明説明（〗63) ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 1 I CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 1 1 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 1 I GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 請 1 I CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 先閱讀背 1 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 1 I CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 1 事 1 1 GTTTGCAAAA GATGTCCAGA TGGGTTCTTC TCAAATGAGA CGTCATCTAA AGCACCCTGT 480 1 I AGAAAACACA CAAATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG AAATGCAACA 540 再填寫 f | CACGACAACA TATGTTCCGG AAACAGTGAA TCAACTCAAA AATGTGGAAT AGATGTTACC 600 本頁 CTGTGTGAGG AGGCATTCTT CAGGTTTGCT GTTCCTACAA AGTTTACGCC TAACTGGCTT 660 1 I AGTGTCTTGG TAGACAATTT GCCTGGCACC AAAGTAAACG CAGAGAGTGT AGAGAGGATA 720 1 1 AAACGGCAAC ACAGCTCACA AGAACAGACT TTCCAGCTGC TGAAGTTATG GAAACATCAA 780 1 I AACAAAGACC AAGATATAGT CAAGAAGATC ATCCAAGATA TTGACCTCTG TGAAAACAGC 340 1 訂 GTGCAGCGGC ACATTGGACA TGCTAACCTC ACCTTCGAGC AGCTTCGTAG CnGrtTGGAA 900 1 I AGCTTACCGG GAAAGAAAGT GGGAGCAGArt GACATTGAAA AAACAATAAA CGCATGCAAA 960 1 1 CCCAGTGACC AGATCCTGAA GCTGCTCAGT TTGTGGCGAA TA/\AAAATGG CGACCAAGAC 1020 1 I ACCTTGAAGG GCCTAATGCA CGCACTAAAG CACTCAAAGA CGTACCACTT TCCCAAAACT 1080 4 1 GTCACTCAGA GTCTAAAGAA GrtCCATCAGG TTCCTTCACA GCTTCACAAT GTACAAATTG 1140 TATCAGAAGT TATTTTTAGA AATGATAGGT AACCAGGTCC AATCAGTAAA AATAAGCTAA 1200 1 1 1 序列號碼：95 1 1 1 序列長度：1 〇 5 6 1 I 序列型：核酸 1 I 鏈數：1 1 1 I 局部解剖狀：直鏈狀 1 1 I 序列種類：cDNA(OCIF-CC) 1 1 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） ^ β 3 3 8 0 7 6 538049 A7 B7 經濟部中央標準局員工消費合作社印製五、發明説明（I64) 1 I 序列： 1 | ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 1 1 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 1 I TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 請 1 1 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 閱讀背面之 1 I CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 1 1 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 注意事項再 1 | CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 1 嚷 GTTTGCAAAA GATGTCCAGA TGGGTTCTTC TCAAATGAGA CGTCATCTAA AGCACCCTGT 480 填寫本頁 AGAAAACACA CAAATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG AAATGCAACA 540 1 I CACGACAACA TATGTTCCGG AAACAGTGAA TCAACTCAAA AATGTGGAAT AGATGTTACC 600 1 1 CTGTGTGAGG AGGCATTCTT CAGGTTTGCT GTTCCTACAA AGTTTACGCC TAACTGGCTT 660 1 I AGTGTCTTGG TAGACAATTT GCCTGGCACC AAAGTAAACG CAGAGAGTGT AGAGAGGATA 720 1 AAACGGCAAC ACAGCTCACA AGAACAGACT TTCCAGCTGC TGAAGTTATG GAAACATCAA 780 訂 I AACAAAGACC AAGATATAGT CAAGAAGATC ATCCAAGATA TTGACCTCTG TGAAAACAGC 340 1 1 GTGCAGCGGC ACATTGGACA TGCTAACCTC ACCTTCGAGC AGCTTCGTAG CTTGATGGAA 900 1 | AGCTTACCGG GAAAGAAAGT GGGAGCAGAA GACATTGAAA ΑΑΑΟΑΛΤΑΛΑ GGCATGCAAA 960 1 ά CCCAGTGACC AGATCCTGAA GCTGCTCAGT TTGTGGCGAA TAAAAAATGG CGACCAAGAC 1020 ACCTTGAAGG GCCTAATGCA CGCACTAAAG CACTGA 1056 1 1 I 序列號碼：96 1 1 1 序列長度：8 1 9 1 1 序列型：核酸 1 1 鏈數：1 1 I 局部解剖狀：直鐽狀 1 1 I 序列種類：c D N A ( 0 C I F - C D D 2 ) 1 1 I 序列： 1 1 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 164 3 8 0 7 6 538049 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明（165) ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 GTTTGCAAAA GATGTCCAGA TGGGTTCTTC TCAAATGAGA CGTCATCTAA AGCACCCTGT 480 AGAAAACACA CAAATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG AAATGCAACA 540 CACGACAACA TATGTTCCGG AAACAGTGAA TCAACTCAAA AATGTGGAAT AGATGTTACC 600 CTGTGTGAGG AGGCATTCTT CAGGTTTGCT GTTCCTACAA AGTTTACGCC TAACTGGCTT 660 AGTGTCTTGG TAGACAATTT GCCTGGCACC AAAGTAAACG CAGAGAGTGT AGAGAGGATA 720 AAACGGCAAC ACAGCTCACA AGAACAGACT TTCCAGCTGC TGAAGTTATG GAAACATCAA 780 AACAAAGACC AAGATATACT CAAGAAGATC ATCCAATGA 819 序列號碼：97 序列長度：594 序列型：核酸鏈數·· 1 局部解剖狀：直鏈狀序列種類：cDNA(OCIF-CDDl) 序列： ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 (請先閱讀背面之注意事項再填寫本頁)1T 4 This paper size applies to Chinese National Standards (CNS) A4 specifications (210X297 mm) 159 3 8 0 7 6 538049 A7 B7 V. Description of invention (160) ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCT 60 CAGGAAACGT TTCCTCCAAA GTACC TTCAT TGTATCGATCAC GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 / GTTTGCAAAT CCGGAAACAG TGAATCAACT CAAAAATGTG GAATAGATGT TACCCTCTGT 480 GAGGAGGCAT TCTTCAGGTT TGCTGTTCCT ACAAAGTTTA CGCCTAACTG GCTTAGTGTC 540 TTGGTAGACA ATTTGCCTGG CACCAAAGTA AACGCAGAGA GTGTAGAGAG GATAAAACGG 600 CAACACAGCT CACAAGAACA GACTTTCCAG CTGCTGAAGT TATGGAAACrt TCAAAACAAA 660 GACCAAGATA TAGTCAAGAA GATCATCCAA GATAHGACC TCTGTGAAAA CAGCGTGCAG 720 CGGCACATTC CACCTTC GAGCAGCTTC GTAGCTTGAT GGAAAGCTTA 780 CCGGGAAAGA AAGTGGGAGC AGAAGACATT GAAAAAACAA TAAAGGCATG CAAACCCAGT 840 GACCAGATCC TGAAGCTGCT CAGTTTGTGG CGAATAAAAA ATGGCGACCA AGACACCTTG 900 AAGGGCCTAA TGCACGCACT AAAGCACTCA AAGACGTACC ACTTTCCCAA AACTGTCACT 960 CAGAGTCTAA AGAAGACCAT CAGGTTCCTT CACAGCTTCA CAATGTACAA ATTGTATCAG 1020 AAGTTATTTT TAGAAATGAT AGGTAACCAG GTCCAATCAG TAAAAATAAG CTGCTTrtTAA 1080 Ministry of Economic Affairs Bureau of Standards staff of consumer cooperatives India (Please read the notes on the back before filling out this page) Sequence number: 9 2 Sequence length: 981 Sequence type: Number of nucleic acid strands: 1 Local anatomy: Linear sequence Type: cDNA (OCIF-DDDl) Sequence: This Paper size applies to Chinese National Standard (CNS) A4 (210X297 mm) 160 38 076 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 538049 A7 B7 V. Description of Invention (1 61) ATGAACAACT TGCTGTGCTG CGCGCTCCTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 GTTTGCAAAA GATGTCCAGA TGGGTTCTTC TCAAATGAGA CGTCATCTAA AGCACCCTGT 480 / AGAAAACACA CAAATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG AAATGCAACA 540 CACGACAACA TATGTTCCGG AAACAGTGAA TCAACTCAAA AATGTGGAAT AGATrtTTGAC 600 CTCTGTGAAA ACAGCGTGCA GCGGCACATT GGACATGCTA ACCTCACCTT CGAGCAGCTT 660 CGTAGCTTGA TGGAAAGCTT ACCGGGAAAG AAAGTGGGAG CAGAAGACAT TGAAAAAACA 720 ATAAAGGCAT GCAAACCCAG TGACCAGATC CTGAAGCTGC TCAGTTTGTG GCGAATrtAAA 730 AATGGCGACC AAGACACCTT GAAGGGCCTA ATGCACGCAC TAAAGCACTC AAAGACGTAC 840 CACTTTCCCA AAACTGTCAC TCAGAGTCTA AAGAAGrtCCA TCAGGTTCCT TCACAGCTTC 900 ACAATGTACA rtATTGTATCA GAAGTTATTT TTAGrtAATGA TAGGTAACCA GGTCCAATCA 960 GTAAAAATAA GCTGCTTATA A 981 sequence Number: 93 sequence length : 984 Sequence type: Nucleic acid strand number: 1 Local anatomy: Linear sequence type · c DNA (0 CIF-DDD 2) Sequence: This paper size applies Chinese National Standard (CNS) A4 specification (210X 297 mm) ^ 3 8 0 7 6 I ----------- (Please read the notes on the back before filling in this page) Order 4 538049 A7 B7 V. Description of the Invention (I62) ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 CATAGGAGCT GCCCTCCTGG ATTTGGAGTG'GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 GTTTGCAAAA GATGTCCAGA TGGGTTCTTC TCAAATGAGA CGTCATCTAA AGCACCCTGT 480 AGAAAACACA CAAATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG AAATGCAACA 540 CACGACAACA TATGTTCCGG AAACAGTGAA TCAACTCAAA AATGT GGAAT AGATGTTACC 600 i CTGTGTGAGG AGGCATTCTT CAGGTTTGCT GTTCCTACAA AGTTTACGCC TAACTGGCTT 660 AGTGTCTTGG TAGACAATTT GCCTGGCACC AAAGTAAACG CAGAGAGTGT AGAGAGGATA 720 AAACGGCAAC ACAGCTCACrt AGAACAGACT TTCCAGCTGC TGAAGTTATG GAAACATCAA 780 AACAAAGACC AAGATATAGT CAAGrtAGATC ATCCAAGACG CACTAAAGCA CTCArtftGACG 840 TACCACTTTC CCAAAACTGT CACTCAGAGT CTAAAGAAGA CCATCAGGTT CCTTCACAGC 900 TTCACAATGT ACAAATTGTA TCAGAAGTTA TTTTTAGAAA TGATAGGTAA CCrtGGTCCAA 960 TCAGTAAAAA TAAGCTGCTT ATAA 984 Sequence number: 94 Sequence length · 1 2 Ο Ο Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling out this page) Sequence type: Nucleic acid chain number: 1 Local anatomy: Linear Sequence type: cDNA (OCIF-CL) Sequence: This paper size applies Chinese National Standard (CNS) A4 specification (210X 297 mm) 162 3 8 0 7 6 538049 A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs Description of the invention (〖63) ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 1 I CAGGAAACG T TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 1 1 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 1 I GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 make 1 I CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 read back 1 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 1 I CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 1 thing 1 1 GTTTGCAAAA GATGTCCAGA TGGGTTCTTC TCAAATGAGA CGTCATCTAA AGCACCCTGT 480 1 I AGAAAACACA CAAATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG AAATGCAACA 540 and then fill f | CACGACAACA TATGTTCCGG AAACAGTGAA TCAACTCAAA AATGTGGAAT AGATGTTACC 600 page CTGTGTGAGG AGGCATTCTT CAGGTTTGCT GTTCCTACAA AGTTTACGCC TAACTGGCTT 660 1 I AGTGTCTTGG TAGACAATTT GCCTGGCACC AAAGTAAACG CAGAGAGTGT AGAGAGGATA 720 1 1 AAACGGCAAC ACAGCTCACA AGAACAGACT TTCCAGCTGC TGAAGTTATG GAAACATCAA 780 1 I AACAAAGACC AAGATATAGT CAAGAAGATC ATCCAAGATA TTGACCTCTG TGAAAACAG C 340 1 set GTGCAGCGGC ACATTGGACA TGCTAACCTC ACCTTCGAGC AGCTTCGTAG CnGrtTGGAA 900 1 I AGCTTACCGG GAAAGAAAGT GGGAGCAGArt GACATTGAAA AAACAATAAA CGCATGCAAA 960 1 1 CCCAGTGACC AGATCCTGAA GCTGCTCAGT TTGTGGCGAA TA / \ AAAATGG CGACCAAGAC 1020 1 I ACCTTGAAGG GCCTAATGCA CGCACTAAAG CACTCAAAGA CGTACCACTT TCCCAAAACT 1080 4 1 GTCACTCAGA GTCTAAAGAA GrtCCATCAGG TTCCTTCACA GCTTCACAAT GTACAAATTG 1140 TATCAGAAGT TATTTTTAGA AATGATAGGT AACCAGGTCC AATCAGTAAA AATAAGCTAA 1200 1 1 1 Sequence number: 95 1 1 1 Sequence length: 1 〇5 6 1 I Sequence type: Nucleic acid 1 I Number of chains: 1 1 1 I Partial anatomy: linear 1 1 I sequence Type: cDNA (OCIF-CC) 1 1 This paper size applies to Chinese National Standard (CNS) A4 (210X297 mm) ^ β 3 3 8 0 7 6 538049 A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs Description of Invention (I64) 1 I Sequence: 1 | ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 1 1 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 1 I TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 Please 1 1 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 Reading 1 I CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG back surface of CAATCGCACC 300 1 1 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 Note again 1 | CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 1 cried GTTTGCAAAA GATGTCCAGA TGGGTTCTTC TCAAATGAGA CGTCATCTAA AGCACCCTGT 480 fill page AGAAAACACA CAAATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG AAATGCAACA 540 1 I CACGACAACA TATGTTCCGG AAACAGTGAA TCAACTCAAA AATGTGGAAT AGATGTTACC 600 1 1 CTGTGTGAGG AGGCATTCTT CAGGTTTGCT GTTCCTACAA AGTTTACGCC TAACTGGCTT 660 1 I AGTGTCTTGG TAGACAATTT GCCTGGCACC AAAGTAAACG CAGAGAGTGT AGAGAGGATA 720 1 AAACGGCAAC ACAGCTCACA AGAACAGACT TTCCAGCTGC TGAAGTTATG GAAACATCAA 780 I AACAAAGACC AAGATATAGT CAAGAAGATC ATCCAAGATA TTGACCTCTG TGAAAACAGC 340 1 1 GTGCAGCGGC ACATTGGACA TGCTAACCTC ACCTTCGAGC AGCTTCGTAG CTTGATGGAA 900 1 | AGCTTACCGG GAAAGAAAGT GGGAGCAGAA GACATTGAAA ΑΑΑΟΑΛΤΑΛΑ GGCATGCAAA 960 1 ά CCCAGTGACC AGATCCTGAA GCTGCTCAGT TTGTGGCGAA TAAAAAATGG CGACCAAGAC 1020 ACCTTGAAGG GCCTAATGCA CGCACTAAAG CACTGA 1056 1 1 I Sequence Number: 96111 sequence length: 81911 Sequence type: Nucleic acid 1 1 Number of strands: 1 1 I Local anatomy: straight cymbal 1 1 I Sequence type: c DNA (0 CIF-CDD 2) 1 1 I Sequence: 1 1 This paper size applies Chinese National Standard (CNS ) A4 specification (210X297 mm) 164 3 8 0 7 6 538049 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention (165) ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAGAG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 CTATACTG CA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 GTTTGCAAAA GATGTCCAGA TGGGTTCTTC TCAAATGAGA CGTCATCTAA AGCACCCTGT 480 AGAAAACACA CAAATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG AAATGCAACA 540 CACGACAACA TATGTTCCGG AAACAGTGAA TCAACTCAAA AATGTGGAAT AGATGTTACC 600 CTGTGTGAGG AGGCATTCTT CAGGTTTGCT GTTCCTACAA AGTTTACGCC TAACTGGCTT 660 AGTGTCTTGG TAGACAATTT GCCTGGCACC AAAGTAAACG CAGAGAGTGT AGAGAGGATA 720 AAACGGCAAC ACAGCTCACA AGAACAGACT TTCCAGCTGC TGAAGTTATG GAAACATCAA 780 AACAAAGACC AAGATATACT CAAGAAGATC ATCCAATGA 819 sequence number: 97 sequence length: OC sequence type: 594 sequence type: 594 sequence type: 594 sequence type: ) Sequence: ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 (Please read the notes on the back before filling this page)

、1T 本紙張尺度適用中國國家標準（CMS ) Α4規格（210Χ297公釐） 165 3 8 0 7 6 538049 經濟部中央檩準局員工消費合作社印製 A7 B7 五、發明説明（〗66) CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG rtGATAGAGIT CTGCTTGAAA 360 CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 GTTTGCAAAA GATGTCCAGA TGGGTTCTTC TCAAATGAGA CGTCATCTAA AGCACCCTGT 480 AGAAAACACA CAAATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG AAATGCAflCA 540 CACGACAACA TATGTTCCGG AAACAGTGAA TCAACTCAAA AATGTGGAAT ATGA 594 序列號碼：98 序列長度：432 序列型：核酸鏈數：1 局部解剖狀：直鏈狀序列種類：cDNA(0CIF-CCR4) 序列： ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCrtArt GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTrtCTAC ACAGACAGCT CGCACACCAG TGACGACTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCrt AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 GTTTGCAAAT GA 432 序列號碼：99 序列長度：3 2 1 序列型：核酸 _數：1 局部解剖狀：直鐽狀 (請先閱讀背面之注意事項再填寫本頁) •罐衣_ 訂本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 166 38 0 76 538049 A7 B7 經濟部中央標準局員工消費合作社印製五、發明説明（1 67 ) 序列種類：c D N A ( 0 C I F - C C R 3 ) 序列： ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG A 321 序列號碼：1 ο ο 序列長度：11 8 2 序列型：核酸鏈數：1 局部解剖狀：直鐽狀序列種類：cDNA(OCIF-CBst) 序列： ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 130 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG CrtAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 GTTTGCAAAA GATGTCCAGA TGGGnCTTC TCAAATGAGA CGTCATCTAA /IGCACCCTGT 430 AGAAAACACA CAAATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG AAATGCAACA 540 CACGACAACA TATGTTCCGG AAACAGTGAA TCAACTCAAA AATGTGGAAT AGATGTTACC 600 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 167 38076 (請先閱讀背面之注意事項再填寫本頁) 經濟部中央標準局員工消費合作社印製 538049 A7 B7 五、發明説明（168) CTGTGTGAGG AGGCATTCTT CAGGHTGCT GTTCCTACAA AGTTTACGCC TAACTGGCTT 660 AGTGTCTTGG TAGACAATTT GCCTGGCACC AAAGTAAACG CAGAGAGTGT AGAGAGGATA 720 AAACGGCAAC ACAGCTCACA AGAACAGACT TTCCAGCTGC TGAAGTTATG GAAACATCAA 780 AACAAAGACC AAGATATAGT CAAGAAGATC ATCCAAGATA TTGACCTCiG TGAAAACAGC 840 GTGCAGCGGC ACATTGGACA TGCTAACCTC ACCTTCGAGC AGCTTCGTAG CTTGATGGAA 900 AGCTTACCGG GAAAGAAAGT GGGAGCAGAA GACATTGAAA AAACAATAAA GGCATGCAAA 960 CCCAGTGACC AGATCCTGAA GCTGCTCAGT TTGTGGCGAA TAAAAAATGG CGACCAAGAC 1020 ACCTTGAAGG GCCTAATGCA CGCACTAAAG CACTCAAAGA CGTACCACTT TCCCAAAACT 1080 GTCACTCAGA GTCTAAAGAA GACCATCAGG TTCCTTCACA GCTTCACAAT GTACAAATTG 1140 TATCAGAAGT TATTTTTAGA AATGATAGGT AACCTAGTCT AG 1182 序列號碼：1 0 1 序列長度：966 序列型：核酸鐽數：1 局部解剖狀：直鏈狀序列種類：cDNA(OCIF-CSph) 序列： ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TrtTGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAArt GTGGAAGACC 130 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGrtGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCHGAAA 360 CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 GTTfGCAAAA GATGTCCAGA TGGGTTCTTC TCAAATGAGA CGTCATCTAA AGCACCCTGT 480 AGAAAACACA CAAATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG AAATGCAACA 540 CACGACAACA TATGTTCCGG AAACAGTGAA TCAACTCAAA AATGTGGAAT AGATGrTACC 600 (請先閲讀背面之注意事項再填寫本頁) 訂 4 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 168 3 8 0 7 6 538049 A7 B7 經濟部中央標準局員工消費合作社印製五、發明説明（1 69 ) 1 I CTGTGTGAGG AGGCATTCTT CAGGTTTGCT GTTCCTACAA AGTTTACGCC TAACTGGCTT 660 1 1 AGTGTCTTGG TAGACAATTT GCCTGGCACC AAAGTAAACG •CAGAGAGTGT AGAGAGGATA 720 1 I AAACGGCAAC ACAGCTCACA AGAACAGACT TTCCAGCTGC TGAAGTTATG GAAACATCAA 730 1 1 AACAAAGACC AAGATATAGT CAAGAAGATC ATCCAAGATA TTGACCTCTG TGAAAACAGC 840 ，、請 1 I 先 1 GTGCAGCGGC ACATTGGACA TGCTAACCTC ACCTTCGAGC AGCTTCGTAG CTTGATGGAA 900 閱讀 1 1 AGCTTACCGG GAAAGAAAGT GGGAGCAGAA GACATTGAAA AAACAATAAA GGCTAGTCTA 960 背面之注意 1 1 GACTAG 966 1 I 序列號碼：102 ψ 項再填 1 % I 序列長度：564 寫本百序列型：核酸只 '^〆 1 1 I 鏈數：1 1 1 I 局部解剖狀：直鏈狀 1 1 訂 1 序列種類：c DNA (0C IF-CBsp) 序列： 1 I ATGArtCAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 1 1 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 1 ά I TGTGACAAAT GTCCTCCTGG TACCTACCTA rtAACAACACT GTACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 1 1 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 1 I CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 1 1 CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 1 I GTTTGCAAAA GATGTCCAGA TGGGTTCTTC TCAAATGAGA CGTCATCTArt AGCACCCTGT 480 1 1 AGAAAACACA CAAATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG AArtTGCAACA 540 1 I CACGACAACA TATGTTCCGG CTAG 564 1 1 1 序列號碼 :103 1 1 I 序列長度 :255 1 1 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） i 6 g 3 8 0 7 6 538049 A7 B7 五、發明説明（l 70 ) 序列型：核酸鏈數：1 局部解剖狀：直鏈狀序列種類：cDNA(OCIF-CPst) 序列： ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT： 240 CTATACCTAG TCTAG 255 序列號碼：1 0 4 序列長度：1 3 1 7 序列型：核酸鐽數：2 局部解剖狀：直鏈狀序列種類：基因D N A (人類0 C I F基因組D N A - 1 ) 序列：經濟部中央檩準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) CTGGAGACAT ATAACTTGAA CACTTGGCCC TGATGGGGAA GCAGCTCTGC AGGGACTTTT 60 TCAGCCATCT GTAAACAATT TCAGTGGCAA CCCGCGAACT GTAATCCATG AATGGGACCA 120 CACTTTACAA GTCATCAAGT CTAACTTCTA GACCAGGGAA TTAATGGGGG AGACAGCGAA 180 CCCTAGAGCA AAGTGCCAAA CHCTGTCGrt TAGCTTGAGG CTAGTGGAAA GACCTCGAGG 240 AGGCTACTCC AGAAGTTCAG CGCGTAGGAA GCTCCGATAC CAATAGCCCT TTGATGATGG 300 TGGGGTTGGT GAAGGGAACA GTGCTCCGCA AGGTTATCCC TGCCCCAGGC AGTCCAATTT 360 TCACTCTGCA GATTCTCTCT GGCTCTAACT ACCCCAGATA ACAAGGAGTG AATGCAGAAT 420 AGCACGGGCT HAGGGCCAA TCAGACATTA GTTAGAAAAA nCCTACTAC ATGGTTTATG 430 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 170 3 8 0 7 6 538049 經濟部中央標準局員工消費合作社印製 A7 B7 ___ 五、發明説明¢71 ) TAAACTTGAA GATGAATGAT TGCGAACTCC CCGAAAAGGG CTCAGACAAT GCCATGCATA 540 AAGAGGGGCC CTGTAATTTG AGGTTTCAGA ACCCGAAGTG AAGGGGTCAG GCAGCCGGGT 600 ACGGCGGAAA CTCACAGCTT TCGCCCAGCG AGAGGACAAA GGTCTGGGAC ACACTCCAAC 660 TGCGTCCGGA TCTTGGCTGG ATCGGACTCT CAGGGTGGAG GAGACACAAG CACAGCAGCT 720 GCCCAGCGTG TGCCCAGCCC TCCCACCGCT GGTCCCGGCT GCCAGGAGGC TGGCCGCTGG 780 CGGGAAGGGG CCGGGAAACC TCAGAGCCCC GCGGAGACAG CAGCCGCCTT GTTCCTCAGC 840 CCGGTGGCTT TTTTTTCCCC TGCTCTCCCA GGGGACAGAC AGCACCGCCC CACCCCTCAC 900 GCCCCACCTC CCTGGGGGAT CCTTTCCGCC CCAGCCCTGA AAGCGTTAAT CCTGGAGCTT 960 TCTGCACACC CCCCGACCGC TCCCGCCCAA GCTTCCTAAA AAAGAAAGGT GCAAAGTTTG 1020 GTCCAGGATA GAAAAATGAC TGATCAAAGG CAGGCGATAC TTCCTGTTGC CGGGACGCTrt 1080 TATATAACGT GATGAGCGCA CGGGCTGCGG AGACGCACCG GAGCGCTCGC CCAGCCGCCG 1140 CCTCCAAGCC CCTGAGGTTT CCGGGGACCrt CA ATG AAC AAG TTG CTG TGC TGC 1193 ile t Asn Lys Leu Leu Cys Cys -20 -15 GCG CTC GIG GTAAGTCCCT GGGCCAGCCC rtCGGGTGCCC GGCGCCTGGG 1242 Λ l a Leu Va l GAGGCTGCTG CCACCTGGTC TCCCAACCTC CCAGCGGACC GGCGGGGAAA AAGGCTCCAC 1302 TCGCTCCCTC CCAAG 1317 序列號碼：1 0 5 序列長度：1 Ο 1 9 Ο 序列型：核酸鏈數：2 局部解剖狀：直鏈狀序列種類：基因DNA(人類OCIF基因組DNA-2) 序列： ________ 本紙張尺度適用中國國家標準（CNS ) A4说格（210X 297公釐） i i 3 8 0 7 6 (請先閱讀背面之注意事項再填寫本頁)、 1T This paper size applies the Chinese National Standard (CMS) A4 specification (210 × 297 mm) 165 3 8 0 7 6 538049 A7 B7 printed by the Consumers' Cooperatives of the Central Procurement Bureau of the Ministry of Economic Affairs 5. Description of the invention (〖66) CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG rtGATAGAGIT CTGCTTGAAA 360 CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 GTTTGCAAAA GATGTCCAGA TGGGTTCTTC TCAAATGAGA CGTCATCTAA AGCACCCTGT 480 AGAAAACACA CAAATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG AAATGCAflCA 540 CACGACAACA TATGTTCCGG AAACAGTGAA TCAACTCAAA AATGTGGAAT ATGA 594 sequence number: 98 sequence length: 432 sequence type: nucleic acid strands: 1 topography shape: linear sequence type: cDNA (0CIF-CCR4) sequence: ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCrtArt GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTrtCTAC ACAGACAGCT CGCACACCAG TGACGACTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCrt AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 GTTTGCAAAT GA Sequence number: 99 Sequence length: 鐽: 1 2 Please pay attention to this page before filling in this page) • Cans _ The size of the paper used in the book is applicable to the Chinese National Standard (CNS) A4 (210X297 mm) 166 38 0 76 538049 A7 B7 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs Description (167) sequence types: c DNA (0 CIF - CCR 3) sequence: ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG A 321 Sequence number: 1 ο ο Sequence length: 11 8 2 Sequence type: Nucleic acid strand number: 1 Local anatomy: Mullion sequence type: cDNA (OCIF-CBst) Sequence: ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAAGCAGGTACTCGTCTACTCCTCTGTACTCGTCTCTACTCGTCTACTCGTCT CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG CrtAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 GTTTGCAAAA GATGTCCAGA TGGGnCTTC TCAAATGAGA CGTCATCTAA / IGCACCCTGT 430 AGAAAACACA CAAATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG AAATGCAACA 540 CACGACAACA TATGTTCCGG AAACAGTGAA TCAACTCAAA AATGTGGAAT AGATGTTACC 600 the present paper Standards are applicable to China National Standard (CNS) A4 specifications (210X 297 mm) 167 38076 (Please read the precautions on the back before filling out this page) Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 538049 A 7 B7 V. invention is described in (168) CTGTGTGAGG AGGCATTCTT CAGGHTGCT GTTCCTACAA AGTTTACGCC TAACTGGCTT 660 AGTGTCTTGG TAGACAATTT GCCTGGCACC AAAGTAAACG CAGAGAGTGT AGAGAGGATA 720 AAACGGCAAC ACAGCTCACA AGAACAGACT TTCCAGCTGC TGAAGTTATG GAAACATCAA 780 AACAAAGACC AAGATATAGT CAAGAAGATC ATCCAAGATA TTGACCTCiG TGAAAACAGC 840 GTGCAGCGGC ACATTGGACA TGCTAACCTC ACCTTCGAGC AGCTTCGTAG CTTGATGGAA 900 AGCTTACCGG GAAAGAAAGT GGGAGCAGAA GACATTGAAA AAACAATAAA GGCATGCAAA 960 CCCAGTGACC AGATCCTGAA GCTGCTCAGT TTGTGGCGAA TAAAAAATGG CGACCAAGAC 1020 ACCTTGAAGG GCCTAATGCA CGCACTAAAG CACTCAAAGA CGTACCACTT TCCCAAAACT 1080 GTCACTCAGA GTCTAAAGAA GACCATCAGG TTCCTTCACA GCTTCACAAT GTACAAATTG 1140 TATCAGAAGT TATTTTTAGA AATGATAGGT AACCTAGTCT AG 1182 serial number: 101 sequence length: 966 sequence type: nucleic acid number Da: 1 local anatomical shape: Type of linear sequence: cDNA (OCIF-CSph) Sequence: ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TrtTGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGAC AAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAArt GTGGAAGACC 130 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGrtGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCHGAAA 360 CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 GTTfGCAAAA GATGTCCAGA TGGGTTCTTC TCAAATGAGA CGTCATCTAA AGCACCCTGT 480 AGAAAACACA CAAATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG AAATGCAACA 540 CACGACAACA TATGTTCCGG AAACAGTGAA TCAACTCAAA AATGTGGAAT AGATGrTACC 600 (Please read the notes on the back before filling out this page) Order 4 This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) 168 3 8 0 7 6 538049 A7 B7 Central Printed by the Consumer Cooperatives of the Standards Bureau. 5. Description of invention (1 69) 1 I CTGTGTGAGG AGGCATTCTT CAGGTTTGCT GTTCCTACAA AGTTTACGCC TAACTGGCTT 660 1 1 AGTGTCTTGG TAGACAATTT GCCTGGCACC AAAGTAAACG • CAGAGAGTGT AGAGAGGATA 720 1 I AAACGGCAACACAGCT CTGC TGAAGTTATG GAAACATCAA 730 1 1 AACAAAGACC AAGATATAGT CAAGAAGATC ATCCAAGATA TTGACCTCTG TGAAAACAGC 840, please 1 I first 1 GTGCAGCGGC ACATTGGACA TGCTAACCTC ACCTTCGAGC AGTCTCGATAG 1 ATCA AAA GTA AAA GCA 900 Read 1 1 AGC AAA GACC Fill in the ψ term 1% I Sequence length: 564 Hundreds of sequence types: Nucleic acid only '^ 〆1 1 I Number of strands: 1 1 1 I Local anatomy: straight 1 1 Order 1 Sequence type: c DNA (0C IF -CBsp) sequence: 1 I ATGArtCAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 1 1 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 1 ά I TGTGACAAAT GTCCTCCTGG TACCTACCTA rtAACAACACT GTACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 1 1 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 1 I CACAACCGCG TGTGCGAATG CA AGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 1 1 CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 1 I GTTTGCAAAA GATGTCCAGA TGGGTTCTTC TCAAATGAGA CGTCATCTArt AGCACCCTGT 480 1 1 AGAAAACACA CAAATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG AArtTGCAACA 540 1 I CACGACAACA TATGTTCCGG CTAG 564 1 1 1 serial number: 103 1 1 I sequence length : 255 1 1 This paper size applies Chinese National Standard (CNS) A4 (210X297 mm) i 6 g 3 8 0 7 6 538049 A7 B7 V. Description of the invention (l 70) Sequence type: Nucleic acid chain number: 1 Local anatomy shape: linear sequence type: cDNA (OCIF-CPst) sequence: ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT: 240 CTATACCTAG TCTAG 255 sequence number : 1 0 4 Sequence length: 1 3 1 7 Sequence type: Nucleic acid number: 2 Local Profile: Linear sequence Type: Gene DNA (human 0 CIF genomic DNA-1) Sequence: Printed by the Consumer Cooperatives of the Central Bureau of Standards, Ministry of Economic Affairs (please read the precautions on the back before filling this page) CTGGAGACAT ATAACTTGAA CACTTGGCCC TGATGGGGAA GCAGCTCTGC AGGGACTTTT 60 TCAGCCATCT GTAAACAATT TCAGTGGCAA CCCGCGAACT GTAATCCATG AATGGGACCA 120 CACTTTACAA GTCATCAAGT CTAACTTCTA GACCAGGGAA TTAATGGGGG AGACAGCGAA 180 CCCTAGAGCA AAGTGCCAAA CHCTGTCGrt TAGCTTGAGG CTAGTGGAAA GACCTCGAGG 240 AGGCTACTCC AGAAGTTCAG CGCGTAGGAA GCTCCGATAC CAATAGCCCT TTGATGATGG 300 TGGGGTTGGT GAAGGGAACA GTGCTCCGCA AGGTTATCCC TGCCCCAGGC AGTCCAATTT 360 TCACTCTGCA GATTCTCTCT GGCTCTAACT ACCCCAGATA ACAAGGAGTG AATGCAGAAT 420 AGCACGGGCT HAGGGCCAA TCAGACATTA GTTAGAAAAA nCCTACTAC ATGGTTTATG 430 This paper size applies to Chinese National Standard (CNS) A4 size (210X 297 mm) 170 3 8 0 7 6 538049 A7 B7 printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs ___ V. Description of the invention ¢ 71) TAAACTTGAA GATGAATGAT TGCGAACTCC CCGAAAAGGG CTCAGACAAT GCCATGCA TA 540 AAGAGGGGCC CTGTAATTTG AGGTTTCAGA ACCCGAAGTG AAGGGGTCAG GCAGCCGGGT 600 ACGGCGGAAA CTCACAGCTT TCGCCCAGCG AGAGGACAAA GGTCTGGGAC ACACTCCAAC 660 TGCGTCCGGA TCTTGGCTGG ATCGGACTCT CAGGGTGGAG GAGACACAAG CACAGCAGCT 720 GCCCAGCGTG TGCCCAGCCC TCCCACCGCT GGTCCCGGCT GCCAGGAGGC TGGCCGCTGG 780 CGGGAAGGGG CCGGGAAACC TCAGAGCCCC GCGGAGACAG CAGCCGCCTT GTTCCTCAGC 840 CCGGTGGCTT TTTTTTCCCC TGCTCTCCCA GGGGACAGAC AGCACCGCCC CACCCCTCAC 900 GCCCCACCTC CCTGGGGGAT CCTTTCCGCC CCAGCCCTGA AAGCGTTAAT CCTGGAGCTT 960 TCTGCACACC CCCCGACCGC TCCCGCCCAA GCTTCCTAAA AAAGAAAGGT GCAAAGTTTG 1020 GTCCAGGATA GAAAAATGAC TGATCAAAGG CAGGCGATAC TTCCTGTTGC CGGGACGCTrt 1080 TATATAACGT GATGAGCGCA CGGGCTGCGG AGACGCACCG GAGCGCTCGC CCAGCCGCCG 1140 CCTCCAAGCC CCTGAGGTTT CCGGGGACCrt CA ATG AAC AAG TTG CTG TGC TGC 1193 ile t Asn Lys Leu Leu Cys Cys -20 -15 GCG CTC GIG GTAAGTCCCT GGGCCAGCCC rtCGGGTGCCC GGCGCCTGGG 1242 Λ la Leu Va l GAGGCTGCTG CCACCTGGTC TCCCAACCTC CCAGCGGACC GGCGGGGAAA AAGGCTCCAC 1302 TCGCTCCCTC CCAAG 1317 serial number : 1 0 5 Sequence length: 1 Ο 1 9 Ο Sequence type: Nucleic acid strand number: 2 Local anatomy: Linear sequence type: Gene DNA (Human OCIF genomic DNA-2) Sequence: ________ This paper size applies to Chinese national standards (CNS) A4 grid (210X 297mm) ii 3 8 0 7 6 (Please read the notes on the back before filling this page)

、1T d 538049 A7 B7 五、發明説明（17 2) GCTTACTTTG TGCCAAATCT CATTAGGCTT AAGGTAATAC AGGACTTTGA GTCAAATGAT 60 ACTGTTGCAC ATAAGAACAA ACCTATTTTC ATGCTAAGAT GATGCCACTG TGTTCCTTTC 120 TCCTTCTAG TTT CTG GAC ATC TCC ATT AAG TGG ACC ACC CAG GAA ACG TTT 1711T d 538049 A7 B7 V. Description of the invention (17 2) GCTTACTTTG TGCCAAATCT CATTAGGCTT AAGGTAATAC AGGACTTTGA GTCAAATGAT 60 ACTGTTGCAC ATAAGAACAA ACCTATTTTC ATGCTAAGAT GATGCCACTG TGTTCCTTTC 120 TCCTTCTAG TTT CTG GAC

Phe Leu Asp lie Ser Ile Lys Trp Thr Thr Gin Glu Thr Phe -10 -5 -1 fl CCT CCA AAG TAC CTT CAT TAT GAC GAA GAA ACC TCT CAT CAG CTG TTG 219Phe Leu Asp lie Ser Ile Lys Trp Thr Thr Gin Glu Thr Phe -10 -5 -1 fl CCT CCA AAG TAC CTT CAT TAT GAC GAA GAA ACC TCT CAT CAG CTG TTG 219

Pro Pro Lys Tyr Leu His Tyr Asp Glu Glu Thr Ser His Gin Lea Leu 5 10 15 , TGT GAC AAA TGT CCT CCT GGT ACC TAC CTA AAA CAA CAC TGT ACA GCA 267Pro Pro Lys Tyr Leu His Tyr Asp Glu Glu Thr Ser His Gin Lea Leu 5 10 15, TGT GAC AAA TGT CCT CCT GGT ACC TAC CTA AAA CAA CAC TGT ACA GCA 267

Cys Asp Lys Cys Pro Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala 20 25 30 35 AAG TGG ArtG ACC GTG TGC GCC CCT TGC CCT GAC CAC TAC TAC ACA GAC 315Cys Asp Lys Cys Pro Pro Gly Thr Tyr Leu Gly His Cys Thr Ala 20 25 30 35 AAG TGG ArtG ACC GTG TGC GCC CCT TGC CCT GAC CAC TAC TAC ACA GAC 315

Lys Trp Lys Thr Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp 40 45 50 AGC TGG CAC ACC AGT GAC GAG TGT CTA TAC TGC AGC CCC GTG TGC AAG 363Lys Trp Lys Thr Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp 40 45 50 AGC TGG CAC ACC AGT GAC GAG TGT CTA TAC TGC AGC CCC GTG TGC AAG 363

Ser Trp His Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys 55 60 65 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) GAG CTG CAG TAC GTC AAG CAG GAG TGC AAT CGC ACC CAC AAC CGC GTG 411Ser Trp His Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys 55 60 65 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (Please read the notes on the back before filling this page) GAG CTG CAG TAC GTC AAG CAG GAG TGC AAT CGC ACC CAC AAC CGC GTG 411

Gla Leu Gin Tyr Val Lys Gin Glu Cys rtsn Arg Thr His Asa Arg Val ·〇 75 80 TGC GAA TGC AAG GAA GGG CGC TAC CTT GAG ATA GAG TTC TGC TTG AAA 459Gla Leu Gin Tyr Val Lys Gin Glu Cys rtsn Arg Thr His Asa Arg Val 〇 75 80 TGC GAA TGC AAG GAA GGG CGC TAC CTT GAG ATA GAG TTC TGC TTG AAA 459

Cys Glu Cys Lys Gla Gly Arg Tyr Leu Glu [le Glu Phe Cys Leu Lys 85 90 95 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 172 3 8 0 7 6 538049 A7 B7 經濟部中央標準局員工消費合作社印製Cys Glu Cys Lys Gla Gly Arg Tyr Leu Glu [le Glu Phe Cys Leu Lys 85 90 95 This paper size applies to the Chinese National Standard (CNS) A4 (210X297 mm) 172 3 8 0 7 6 538049 A7 B7 Central Standard of the Ministry of Economic Affairs Printed by Bureau Consumers Cooperative

五、發明説明（17 3) CAT AGG AGC TGC CCT CCT GGA TTT GGA GTG GTG CAA GCT G GTACGTGTCA His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala 100 105 110 ATGTGCAGCA AAATTAATTA GGATCATGCA AAGTCAGATA GTTGTGACAG TTTAGGAGAA CACTTTTGTT CTGATGACAT TATAGGATAG CAAATTGCAA AGGTAATGAA ACCTGCCAGG y TAGGTACTAT GTGTCTGGAG TGCTTCCAAA GGACCATTGC TCAGAGGAAT ACTTTGCCAC TACAGGGCAA TTTAATGACA AATCTCAAAT GCAGCAAATT ATTCTCTCAT GAGATGCrtTG ATGGTTTTTT TTTTTTTTTT TAAAGAAACA AACTCAAGTT GCACTATTGA TAGTTGATCT ATACCTCTAT ATTTCACTTC AGCATGGACA CCTTCAAACT GCAGCACTTT TTGACAAACA TCAGAAATGT ΤΛΑΐΤΤΑΤΛΟ CAAGrtGAGTA ATTATGCTCA TATTrt/UGAG ACTOTGCAGT GCTAACAATA AGCAGTTATA ATTArtTTATG TAAAArtATGA GAATGGTGAG GGGAATTGCA TTTCATTATT AAAAACAAGG CTAGTTCTTC CTTTrtGCATG GGAGCTGAGT GTTTGGGAGG GTAAGGACTA TAGCAGAATC TCTTCAATGA GCTTATTCTT TATCTTAGAC AAAACAGATT GTCAAGCCAA GAGCAAGCAC TTGCCTATAA ACCAAGTGCT TTCTCTTTTG CATTTTGAAC AGCATTGGTC AGGGCTCATG TGTATTGAAT CTTTTAAACC AGTAACCCAC GTTTTTTTTC TGCCACATTT GCGAAGCTTC AGTGCAGCCT ATAACTTTTC ATAGCTTGAG AAAATTAAGA GTATCCACTT AGTTAGATGG AAGAAGTAAT CAGTATAGAT TCTGATGACT CAGTTTGAAG CAGTGTTTCT CAACTGAAGC CCTGCTGATA TTTTAAGAAA TATCTGGATT CCTAGGCTGG ACTCCTTTTT GTGGGCAGCT GTCCTGCGCA TTGTAGAATT TTGGCAGCAC CCCTGGACTC TAGCCACTAG ATACCAATAG CAGTCCTTCC CCCATGTGAC AGCCAAAAAT GTCTTCAGAC ACTGTCAAAT GTCGCCAGGT GGCAAAATCA CTCCTGGTTG AGAACAGGGT CATCAATGCT AAGTATCTGT AACTATTTTA ACTCTCAAAA CTTGTGATAT ACAAAGTCTA AATTATTAGA CGACCAATAC TTTAGGTTTA AAGGCATACA AATGAAACAT TCAAAAATCA AAATCTATTC TGTTTCTCAA ATAGTGAATC TTATAAAATT AATCACAGAA GATGCAAATT GCATCAGAGT CCCTTAAAAT TCCTCTTCGT ATGAGTATTT GAGGGAGGAA TTGGTGATAG TTCCTACTIT CTATTGGATG GTACHTGAG'ACTCAAAAGC TAAGCTAAGT TGTGTGTGTG TCAGGGTGCG GGGTGTGGAA TCCCATCAGA TAAAAGCAAA TCCATGTAAT TCATTCAGTA AGTTGTATAT 2 8 4 ο 6 2 6 6 7 8 8 9 9 6 2 84OCJ62004O6 2 —- 2 2344-0 56778 (請先閲讀背面之注意事項再填寫本頁)V. Description of the invention (17 3) CAT AGG AGC TGC CCT CCT GGA TTT GGA GTG GTG CAA GCT G GTACGTGTCA His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala 100 105 110 ATGTGCAGCA AAATTAATTA GGATCATGCA AAGTCAGATA GTTGTGACAG TTTAGGAGA CTA ACCTGCCAGG y TAGGTACTAT GTGTCTGGAG TGCTTCCAAA GGACCATTGC TCAGAGGAAT ACTTTGCCAC TACAGGGCAA TTTAATGACA AATCTCAAAT GCAGCAAATT ATTCTCTCAT GAGATGCrtTG ATGGTTTTTT TTTTTTTTTT TAAAGAAACA AACTCAAGTT GCACTATTGA TAGTTGATCT ATACCTCTAT ATTTCACTTC AGCATGGACA CCTTCAAACT GCAGCACTTT TTGACAAACA TCAGAAATGT ΤΛΑΐΤΤΑΤΛΟ CAAGrtGAGTA ATTATGCTCA TATTrt / UGAG ACTOTGCAGT GCTAACAATA AGCAGTTATA ATTArtTTATG TAAAArtATGA GAATGGTGAG GGGAATTGCA TTTCATTATT AAAAACAAGG CTAGTTCTTC CTTTrtGCATG GGAGCTGAGT GTTTGGGAGG GTAAGGACTA TAGCAGAATC TCTTCAATGA GCTTATTCTT TATCTTAGAC AAAACAGATT GTCAAGCCAA GAGCAAGCAC TTGCCTATAA ACCAAGTGCT TTCTCTTTTG CATTTTGAAC AGCATTGGTC AGGGCTCATG TGTATTGAAT CTTTTAAACC AGTAACCCAC GTTTTTTTTC TGCCACATTT GCGAAGCTTC AGTGCAGCCT A TAACTTTTC ATAGCTTGAG AAAATTAAGA GTATCCACTT AGTTAGATGG AAGAAGTAAT CAGTATAGAT TCTGATGACT CAGTTTGAAG CAGTGTTTCT CAACTGAAGC CCTGCTGATA TTTTAAGAAA TATCTGGATT CCTAGGCTGG ACTCCTTTTT GTGGGCAGCT GTCCTGCGCA TTGTAGAATT TTGGCAGCAC CCCTGGACTC TAGCCACTAG ATACCAATAG CAGTCCTTCC CCCATGTGAC AGCCAAAAAT GTCTTCAGAC ACTGTCAAAT GTCGCCAGGT GGCAAAATCA CTCCTGGTTG AGAACAGGGT CATCAATGCT AAGTATCTGT AACTATTTTA ACTCTCAAAA CTTGTGATAT ACAAAGTCTA AATTATTAGA CGACCAATAC TTTAGGTTTA AAGGCATACA AATGAAACAT TCAAAAATCA AAATCTATTC TGTTTCTCAA ATAGTGAATC TTATAAAATT AATCACAGAA GATGCAAATT GCATCAGAGT CCCTTAAAAT TCCTCTTCGT ATGAGTATTT GAGGGAGGAA TTGGTGATAG TTCCTACTIT CTATTGGATG GTACHTGAG'ACTCAAAAGC TAAGCTAAGT TGTGTGTGTG TCAGGGTGCG GGGTGTGGAA TCCCAT 6 6 2 8 6 2 8 8GTGTATA (Please fill in this page again)

、1T 4 本紙張尺度適用中國國家標準（CNS ) A4規格（21 OX 297公釐） 173 3 8 0 7 6 經濟部中央標準局員工消費合作社印製 538049 A7 B7 五、發明説明（174)、 1T 4 This paper size applies to Chinese National Standard (CNS) A4 specification (21 OX 297 mm) 173 3 8 0 7 6 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 538049 A7 B7 V. Description of the invention (174)

GTAGAAAAAT GAAAAGTGGG CTATGCAGCT TGGAAACTAG AGAATTTTGA AAAATAATGG AAATCACAAG GATCTTTCTT AAATAAGTAA GAAAATCTGT TTGTAGAATG AAGCAAGCAG GCAGCCAGAA GACTCAGAAC AAAAGTACAC ATTTTACTCT GTGTACACTG GCAGCACAGT GGGATTTATT TACCTCTCCC TCCCTArtAAA CCCACACAGC GGTTCCTCTT GGGAAATAAG AGGTTTCCAG CCCAAAGAGA AGGAAAGACT ATGTGGTGTT ACTCTAArtAA GTATTTAATA ACCGTTTTGT TGTTGCTGTT GCTGTTTTGA AATCAGATTG TCTCCTCTCC ATATTTTATT /GTAGAAAAAT GAAAAGTGGG CTATGCAGCT TGGAAACTAG AGAATTTTGA AAAATAATGG AAATCACAAG GATCTTTCTT AAATAAGTAA GAAAATCTGT TTGTAGAATG AAGCAAGCAG GCAGCCAGAA GACTCAGAAC AAAAGTACAC ATTTTACTCT GTGTACACTG GCAGCACAGT GGGATTTATT TACCTCTCCC TCCCTArtAAA CCCACACAGC GGTTCCTCTT GGGAAATAAG AGGTTTCCAG CCCAAAGAGA AGGAAAGACT ATGTGGTGTT ACTCTAArtAA GTATTTAATA ACCGTTTTGT TGTTGCTGTT GCTGTTTTGA AATCAGATTG TCTCCTCTCC ATATTTTATT /

TACTTCATTC TGTTAATTCC TGTGGAATTA CTTAGAGCAA GCATGGTGAA TTCTCAACTG TAAAGCCAAA TTTCTCCATC ΑΤΤΑΤΛΑΤΤΤ CACATTTTGC CTGGCAGGTT ATAATHTTA TATTTCCACT GATAGTAATA AGGTAAAATC ATTACTTAGA TGGATAGATC TTTTTCATA/\ AAAGTACCAT CAGTTATAGA CGGAAGTCAT GTTCATGTTC AGGAAGGTCA TTAGATAAAG CTTCTGAATA TAHATGAAA CrtTTAGTTCT GTCATTCTTA GATTCTTTTT GTTAAATAAC TTTAAAAGCT AACTTACCTA AAAGrtAATAT CTGACACATA TGAACTTCTC ATTAGGATGCTACTTCATTC TGTTAATTCC TGTGGAATTA CTTAGAGCAA GCATGGTGAA TTCTCAACTG TAAAGCCAAA TTTCTCCATC ΑΤΤΑΤΛΑΤΤΤ CACATTTTGC CTGGCAGGTT ATAATHTTA TATTTCCACT GATAGTAATA AGGTAAAATC ATTACTTAGA TGGATAGATC TTTTTCATA / \ AAAGTACCAT CAGTTATAGA CGGAAGTCAT GTTCATGTTC AGGAAGGTCA TTAGATAAAG CTTCTGAATA TAHATGAAA CrtTTAGTTCT GTCATTCTTA GATTCTTTTT GTTAAATAAC TTTAAAAGCT AACTTACCTA AAAGrtAATAT CTGACACATA TGAACTTCTC ATTAGGATGC

AGGAGAAGAC CCAAGCCACA GATATGTATC TGAAGAATGA ACAAGATTCT TAGGCCCGGC ACGLTGGCTC ACATCTGTAA TCTCAAGAGT TTGrtGAGGTC AAGGCGGGCA GrtTCACCTGA GGTCAGGAGT TCAAGACCAG CCTGGCCAAC ATGATGAAAC CCTGCCTCTA CTAAAAATAC AAAAATTAGC AGGGCATGGT GGTGCATGCC TGCAACCCTA GCTACTCAGG AGGCTGAGAC AGGAGAATCT CTTGAACCCT CGAGGCGGAG GTTGTGGTGA GCTGAGATCC CTCTACTGCA CTCCAGCCTG GGTGACAGAG ATGAGACTCC GTCCCTGCCG CCGCCCCCGC CTTCCCCCCC AAAAAGATTC TTCTTCATGC AGAACATACG GCAGTCAACA AAGGGAGACC TGGGTCCAGG TGTCCAAGTC ACTTATTTCG AGTAAATTAG CAATGAAAGA ATGCCATGGA ATCCCTGCCC AAATACCTCT GCTTATGATA TTGTAGAATT TGATATAGAG TTGTATCCCA TTTAAGGAGT AGGATGTAGT AGGAAAGTAC TAAAAACAAA CACACAAACA GAAAACCCTC TTTGCTTTGT AAGGTGGTTC CTAAGATAAT GTCAGTGCAA TGCTGGAAAT ΑΑΤΑΤΤΤΛΑΤ ATGTGAAGGT TTTAGGCTGT GTTTTCCCCT CCTGTTCTTT TTTTCTGCCA GCCCTTTGTC ATTTTTGCAG GTCAATGAAT CATGTAGAAA GAGACAGGAG ATGAAACTAG AACCAGTCCA TTTTGCCCCT TTTTTTATTT TCTGGTTTTG GTAAAAGATA CAATGAGGTA GGAGGTTGAG ΑΤΤΤΑΓΑΑΑΤ GAAGTTTAAT AAGTTTCTGT AGCTTTGATT TTTCTCTTTC ATATTTGTTA TCTTGCATAA GCCAGAATTG GCCTGTAAAA TCTACATATG GATATTGAAG TCTAAATCTG TTCAACTAGC 99999999999 9999999999999999 62840628406 2840628406 2 8406 O.W ο 1 —-23344566 7 7 8 9 9 0 0 —12 2 334556 222 2 222222 2 9^ 222 2 3333 οϋ 333333 (請先閲讀背面之注意事項再填寫本頁) 本紙張尺度適用中國國家標準（CNS ) Α4規格（210 X 297公釐） 174 3 8 0 7 6 538049 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明（1 7 5) TTACACTAGA TGGAGATATT TTCATATTCA GATACACTGG AATGTATGAT CTAGCCATGC 3689 GTAATATAGT CAAGTGTTTG AAGGTATTTA TTTTTAATAG CGTCTTTAGT TGTGGACTGG 3749 TTCAAGTTTT TCTGCCAATG ATTTCTTCAA ATTTATCAAA TATTTTTCCA TCATGAAGTA 3809 AAATGCCCTT GCAGTCAGCC TTCCTGAAGT TTGAACGACT CTGCTGTTTT AAACAGTTTA 3869 AGCAAATGGT ATATCATCTT CCGTTTACTA TGTAGCTTAA CTGCAGGCTT ACGCTTTTGA 3929 GTCAGCGGCC AACTTTATTG CCACCTTCAA AAGTTTATTA TAATGTTGTA AATTTTTACT 3989 / TCTCAAGGTT AGCATACTTA GGAGTTGCTT CACAATTAGG ATTCAGGAAA GAAAGAACTT 4049 CAGTAGGAAC TGATTGGAAT TTAATGATGC AGCATTCAAT GGGTACTAAT TTCAAAGAAT 4109 GATATTACAG CAGACACACA GCAGTTATCT TGATTTTCTA GGAATAATTG TATGAAGAAT 4169 ATGGCTGACA ACACGGCCTT ACTGCCACTC AGCGGAGGCT GGACTAATGA ACACCCTACC 4229 CTTCTTTCCT TTCCTCTCAC ATTTCATGAG CGTTTTGTAG GTAACGAGAA AATTGACTTG 4239AGGAGAAGAC CCAAGCCACA GATATGTATC TGAAGAATGA ACAAGATTCT TAGGCCCGGC ACGLTGGCTC ACATCTGTAA TCTCAAGAGT TTGrtGAGGTC AAGGCGGGCA GrtTCACCTGA GGTCAGGAGT TCAAGACCAG CCTGGCCAAC ATGATGAAAC CCTGCCTCTA CTAAAAATAC AAAAATTAGC AGGGCATGGT GGTGCATGCC TGCAACCCTA GCTACTCAGG AGGCTGAGAC AGGAGAATCT CTTGAACCCT CGAGGCGGAG GTTGTGGTGA GCTGAGATCC CTCTACTGCA CTCCAGCCTG GGTGACAGAG ATGAGACTCC GTCCCTGCCG CCGCCCCCGC CTTCCCCCCC AAAAAGATTC TTCTTCATGC AGAACATACG GCAGTCAACA AAGGGAGACC TGGGTCCAGG TGTCCAAGTC ACTTATTTCG AGTAAATTAG CAATGAAAGA ATGCCATGGA ATCCCTGCCC AAATACCTCT GCTTATGATA TTGTAGAATT TGATATAGAG TTGTATCCCA TTTAAGGAGT AGGATGTAGT AGGAAAGTAC TAAAAACAAA CACACAAACA GAAAACCCTC TTTGCTTTGT AAGGTGGTTC CTAAGATAAT GTCAGTGCAA TGCTGGAAAT ΑΑΤΑΤΤΤΛΑΤ ATGTGAAGGT TTTAGGCTGT GTTTTCCCCT CCTGTTCTTT TTTTCTGCCA GCCCTTTGTC ATTTTTGCAG GTCAATGAAT CATGTAGAAA GAGACAGGAG ATGAAACTAG AACCAGTCCA TTTTGCCCCT TTTTTTATTT TCTGGTTTTG GTAAAAGATA CAATGAGGTA GGAGGTTGAG ΑΤΤΤΑΓΑΑΑΤ GAAGTTTAAT AAGTTTCTGT AGCTTTGATT TTTCTCTTTC ATATTTGTTA TCTTGCATAA GCCAGAATTG GCCTGTAAAA TCTACATATG GATATTGAAG TCTAAATCTG TTCAACTAGC 99999999999 9999999999999999 62840628406 2840628406 2 8406 OW ο 1 —-23344566 7 7 8 9 9 0 0 —12 2 334556 222 2 222222 2 9 ^ 222 2 3333 (Please read the back page again) ϋ 333 (Fill in this page) This paper size is in accordance with Chinese National Standard (CNS) A4 (210 X 297 mm) 174 3 8 0 7 6 538049 A7 B7 printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (1 7 5 ) TTACACTAGA TGGAGATATT TTCATATTCA GATACACTGG AATGTATGAT CTAGCCATGC 3689 GTAATATAGT CAAGTGTTTG AAGGTATTTA TTTTTAATAG CGTCTTTAGT TGTGGACTGG 3749 TTCAAGTTTT TCTGCCAATG ATTTCTTCAA ATTTATCAAA TATTTTTCCA TCATGAAGTA 3809 AAATGCCCTT GCAGTCAGCC TTCCTGAAGT TTGAACGACT CTGCTGTTTT AAACAGTTTA 3869 AGCAAATGGT ATATCATCTT CCGTTTACTA TGTAGCTTAA CTGCAGGCTT ACGCTTTTGA 3929 GTCAGCGGCC AACTTTATTG CCACCTTCAA AAGTTTATTA TAATGTTGTA AATTTTTACT 3989 / TCTCAAGGTT AGCATACTTA GGAGTTGCTT CACAATTAGG ATTCAGGAAA GAAAGAACTT 4049 CAGTAGGAAC TGATTGGAAT TTAATGATGC AG CATTCAAT GGGTACTAAT TTCAAAGAAT 4109 GATATTACAG CAGACACACA GCAGTTATCT TGATTTTCTA GGAATAATTG TATGAAGAAT 4169 ATGGCTGACA ACACGGCCTT ACTGCCACTC AGCGGAGGCT GGACTAATGA ACACCCTACC 4229 CTTCTTTCCT TTCCTCACTAC ATTCAT

CrtTTTGCATT ACArtGGAGGrt GAAACTGGCA AAGGGGATGA TGGTGGAAGT TTTGTTCTGT 4349 CTAATGAAGT GAAAAATGrtA AATGCTAGAG TTTTGTGCAA CATAATAGTA GCAGTAAAAA 4409 CCA^GTGAAA AGTCTTTCCA AArtCTGTGTT AAGAGGGCAT CTGCTGGGAA ACGATTTGAG 4469 GAGAAGGTAC TAAATTGCTT GGTATTTTCC GTAG GA ACC CCA GAG CGA AAT ACA 4523CrtTTTGCATT ACArtGGAGGrt GAAACTGGCA AAGGGGATGA TGGTGGAAGT TTTGTTCTGT 4349 CTAATGAAGT GAAAAATGrtA AATGCTAGAG TTTTGTGCAA CATAATAGTA GCAGTAAAAA 4409 CCA ^ GTGAAA CATCAGTCACGCGCGCGCGCGCGCGCGCGCGCGCTGGCGCGCGCTGGCGCGCGCTGGCGCGCGCTGGCGCGCGCTGGCGCGCGCTGGCGCGCGCTGGCGCGCGCTGGC

Gly Thr Pro Glu Arg Asn Thr 115 GTT TGC AAA AGA TGT CCA GAT GGG TTC TTC TCA AAT GAG ACG TCA TCT 4571Gly Thr Pro Glu Arg Asn Thr 115 GTT TGC AAA AGA TGT CCA GAT GGG TTC TTC TCA AAT GAG ACG TCA TCT 4571

Val Cys Lys Arg Cys Pro Asp Gly Phe Phe Ser Asn Gla Thr Ser Ser 120- 125 130 135 AAA GCA CCC TGT AGA AAA CAC ACA AAT TGC ACT GTC TTT GGT CTC CTG 4619Val Cys Lys Arg Cys Pro Asp Gly Phe Phe Ser Asn Gla Thr Ser Ser 120- 125 130 135 AAA GCA CCC TGT AGA AAA CAC ACA AAT TGC ACT GTC TTT GGT CTC CTG 4619

Lys Ala Pro Cys Arg Lys His Thr Asn Cys Ser Val Phe Gly Lea Leu 140 145 150 CTA ACT CAG AAA GGA AAT GCA ACA CAC GAC AAC ATA TGT TCC GGA AAC 4667Lys Ala Pro Cys Arg Lys His Thr Asn Cys Ser Val Phe Gly Lea Leu 140 145 150 CTA ACT CAG AAA GGA AAT GCA ACA CAC GAC AAC ATA TGT TCC GGA AAC 4667

Leu Thr Gin Lys Gly Asn Ala Thr His Asp Asn lie Cys Ser Gly Asn 155 160 165 (請先閲讀背面之注意事項再填寫本頁) 訂 d 本紙張尺度適用中國國家標準（CNS ) A4規格（210 X297公釐） 175 3 8 0 7 6 538049 經濟部中央標準局員工消費合作衽印製 A7 B7 五、發明説明（176) AGT GAA TCA ACT CAA AAA TGT GGA ΑΤΑ G GTAATTACAT TCCAAAATAC 4715Leu Thr Gin Lys Gly Asn Ala Thr His Asp Asn lie Cys Ser Gly Asn 155 160 165 (Please read the notes on the back before filling out this page) Order d This paper size applies to the Chinese National Standard (CNS) A4 specification (210 X297) 175) 175 3 8 0 7 6 538049 Consumption cooperation between employees of the Central Bureau of Standards of the Ministry of Economic Affairs and printing A7 B7 V. Description of the invention (176) AGT GAA TCA ACT CAA AAA TGT GGA ΑΤΑ G GTAATTACAT TCCAAAATAC 4715

Ser Glu Ser Thr Gin Lys Cys Gly lie 170 175 GTCTTTGTAC GATTTTGTAG TATCATCTCT CTCTCTGAGT TGAACACAAG GCCTCCAGCC 4775 ACATTCTTGG TCAAACTTAC ATTTTCCCTT TCTTGAATCT TAACCAGCTA AGGCTACTCT 4835 CGATGCATTA CTGCTAAAGC TACCACTCAG AATCTCTCAA AAACTCATCT TCTCACAGAT 4895 AACACCTCAA AGCTTGATTT TCTCTCCTTT CACACTGAAA TCAAATCTTG CCCATAGGCA 4955 AAGGGCAGTG TCAAGTTTGC CACTGAGATG AAATTAGGAG AGTCCAAACT GTAGrtATTCA 5015 CGTTGTGTGT TATTACTTTC ACGArtTGTCT GTATT/VrTAA CTAArtGTATA TATTGGCAAC 5075 TAAGAAGCAA AGTGATATAA ACATGATGAC AAATTAGGCC AGGCATGGTG GCTTACTCCT 5135 ATA)\TCCCA/\ CATTTTGGGG GGCCAAGGTA GGCAGATCAC TTGAGGTCAG GATTTCAAGA 5195 CCAGCCTGAC CAACATCGTG AAACCTTGTC TCTACTAAAA ATACAAAAAT TAGCTGGGCA 5255 TGGTAGCAGG CACTTCTAGT ACCAGCTACT CAGGGCTGAG GCAGGAGAAT CGCTTGAACC 5315 CAGGAGATGG AGGTTGCAGT GAGCTGAGAT TGTACCACTG CACTCCAGTC TGGGCAACAG 5375 AGCAAGATTT CATCACACAC ACACACACAC ACACACACAC ACACATTrtGA AATGTGTACT 5435 TGGCTTTGTT ACCTATGGTA TTAGTGCATC TATTGCATGG A:\CTTCCAAG CTACTCTGGT 5495 TGTGTTAAGC TCTTCATTGG GTACAGGTCA CTAGTATTAA GTTCAGGTTA TTCGGATGCA 5555 TTCCACGGTA GTGATGACAA TTCATCAGGC TAGTGTGTGT GTTCACCTTG TCACTCCCAC 5615 CACTAGACTA ATCTCAGACC TTCACTCAAA GACACATTAC ACTAAAGATG ATTTGCTTTT 5675 TTGTGTTTAA TCAAGCAATG GTATAAACCA GCTTGACTCT CCCCAAACAG TTTTTCGTAC 5735 TACAAAGAAG TTTATGAAGC AGAGAAATGT GAATTGATAT ATATATGAGA nCTAACCCA 5795 GTTCCAGCAT TGTTTCATTG TGTAATTGAA ATCATAGACA AGCCATTTTA GCCTTTGCTT 5855 TCTTATCTAA AAAAAAAAAA AAAAAAATGA AGGAAGGGGT ATTAAAAGGA GTGATCAAAT 59L5 TTTAACATTC TCTTTAATTA ATTCATTTTT AATTTTACTT TTTTTCATTT ATTGTGCACT 5975 TACTATGTGG TACTGTGCTA TAGAGGCTTT AACATTTATA AAAACACTGT GAAAGTTGCT 6035 TCAGATGAAT ATAGGTAGTA GAACGGCAGA ACTAGTATTC AAAGCCAGGT CTGATGAATC 6095 CAAAAACAAA CACCCATTAC TCCCATTTTC TGGGACATAC TTACTCTACC CAGATGCTCT 6155 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） (請先閲讀背面之注意事項再填寫本頁)Ser Glu Ser Thr Gin Lys Cys Gly lie 170 175 GTCTTTGTAC GATTTTGTAG TATCATCTCT CTCTCTGAGT TGAACACAAG GCCTCCAGCC 4775 ACATTCTTGG TCAAACTTAC ATTTTCCCTT TCTTGAATCT TAACCAGCTA AGGCTACTCT 4835 CGATGCATTA CTGCTAAAGC TACCACTCAG AATCTCTCAA AAACTCATCT TCTCACAGAT 4895 AACACCTCAA AGCTTGATTT TCTCTCCTTT CACACTGAAA TCAAATCTTG CCCATAGGCA 4955 AAGGGCAGTG TCAAGTTTGC CACTGAGATG AAATTAGGAG AGTCCAAACT GTAGrtATTCA 5015 CGTTGTGTGT TATTACTTTC ACGArtTGTCT GTATT / VrTAA CTAArtGTATA TATTGGCAAC 5075 TAAGAAGCAA AGTGATATAA ACATGATGAC AAATTAGGCC AGGCATGGTG GCTTACTCCT 5135 ATA) \ TCCCA / \ CATTTTGGGG GGCCAAGGTA GGCAGATCAC TTGAGGTCAG GATTTCAAGA 5195 CCAGCCTGAC CAACATCGTG AAACCTTGTC TCTACTAAAA ATACAAAAAT TAGCTGGGCA 5255 TGGTAGCAGG CACTTCTAGT ACCAGCTACT CAGGGCTGAG GCAGGAGAAT CGCTTGAACC 5315 CAGGAGATGG AGGTTGCAGT GAGCTGAGAT TGTACCACTG CACTCCAGTC TGGGCAACAG 5375 AGCAAGATTT CATCACACAC ACACACACAC ACACACACAC ACACATTrtGA AATGTGTACT 5435 TGGCTTTGTT ACCTATGGTA TTAGTGCATC TATTGCATGG A: \ CTTCCAAG CTACTCTGGT 5495 TGTGTTAAGC T CTTCATTGG GTACAGGTCA CTAGTATTAA GTTCAGGTTA TTCGGATGCA 5555 TTCCACGGTA GTGATGACAA TTCATCAGGC TAGTGTGTGT GTTCACCTTG TCACTCCCAC 5615 CACTAGACTA ATCTCAGACC TTCACTCAAA GACACATTAC ACTAAAGATG ATTTGCTTTT 5675 TTGTGTTTAA TCAAGCAATG GTATAAACCA GCTTGACTCT CCCCAAACAG TTTTTCGTAC 5735 TACAAAGAAG TTTATGAAGC AGAGAAATGT GAATTGATAT ATATATGAGA nCTAACCCA 5795 GTTCCAGCAT TGTTTCATTG TGTAATTGAA ATCATAGACA AGCCATTTTA GCCTTTGCTT 5855 TCTTATCTAA AAAAAAAAAA AAAAAAATGA AGGAAGGGGT ATTAAAAGGA GTGATCAAAT 59L5 TTTAACATTC TCTTTAATTA ATTCATTTTT AATTTTACTT TTTTTCATTT ATTGTGCACT 5975 TACTATGTGG TACTGTGCTA TAGAGGCTTT AACATTTATA AAAACACTGT GAAAGTTGCT 6035 TCAGATGAAT ATAGGTAGTA GAACGGCAGA ACTAGTATTC AAAGCCAGCT (China National Standards CATCACCTCTCTCTCTCTCTCTCTCTCTCT (Please fill in this page again)

、?T d 176 3 8 0 7 6 經濟部中央標準局員工消費合作社印製 538049 A7 B7 五、發明説明（177) GGGCTTTGTA ATGCCTATGT AAATAACATA GTTTTATGTT TGGTTATTTT CCTATGTAAT 6215 GTCTACTTAT ATATCTGTAT CTATCTCTTG CTTTGTTTCC AAAGGTAAAC TATGTGTCTA 6275 AATGTGGGCA AAAAATAACA CACTATTCCA AATTACTGTT CAAATTCCTT TAAGTCAGTG 6335 ATAATTATTT GTTTTGACAT TAATCATGAA GTTCCCTGTG GGTACTAGGT AAACCTTTAA 6395 TAGAATGTTA ATGTTTGTAT TCATTrtTAAG AATTTTTGGC TGTTACTTAT TTACrtACAAT 6455 ATTTCACTCT AATTAGACAT TTACTAAACT TTCTCTTGAA AACAATGCCC AAAAAAGAAC 6515 ATTAGAAGAC ACGTAAGCTC AGTTGGTCTC TGCCACTAAG ACCAGCCAAC AGAAGCTTGA 6575 TTTTATTCAA ACTTTGCATT TTAGCATATT TTATCTTGGA AAATTCAATT GTGTTGGTTT 6635 TTTGTTTTTG TTTGT/VrTGA ATAGACTCTC rtGArtATCCAA TTGiTGAGTA ArtTCTTCTGG 6695 GHTTCTAAC CTTTCTTTAG AT GTT ACC CTG TGT GrtG GAG GCA TTC TTC AGG 6747,? D 176 3 8 0 7 6 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 538049 A7 B7 V. Description of the invention (177) GGGCTTTGTA ATGCCTATGT AAATAACATA GTTTTATGTT TGGTTATTTT CCTATGTAAT 6215 GTCTACTTAT ATATCTCATCACATA CTA ATGTA CTA 6335 ATAATTATTT GTTTTGACAT TAATCATGAA GTTCCCTGTG GGTACTAGGT AAACCTTTAA 6395 TAGAATGTTA ATGTTTGTAT TCATTrtTAAG AATTTTTGGC TGTTACTTAT TTACrtACAAT 6455 ATTTCACTCT AATTAGACAT TTACTAAACT TTCTCTTGAA AACAATGCCC AAAAAAGAAC 6515 ATTAGAAGAC ACGTAAGCTC AGTTGGTCTC TGCCACTAAG ACCAGCCAAC AGAAGCTTGA 6575 TTTTATTCAA ACTTTGCATT TTAGCATATT TTATCTTGGA AAATTCAATT GTGTTGGTTT 6635 TTTGTTTTTG TTTGT / VrTGA ATAGACTCTC rtGArtATCCAA TTGiTGAGTA ArtTCTTCTGG 6695 GHTTCTAAC CTTTCTTTAG AT GTT ACC CTG TGT GrtG GAG GCA TTC TTC AGG 6747

Asp Val Thr Leu Cys Glu Glu Ala Phe Phe Arg ' 180 185 TTT GCT GTT CCT ACA AAG TTT ACG CCT AAC TGC CTT AGT GTC TTG GTA 6795Asp Val Thr Leu Cys Glu Glu Ala Phe Phe Arg '180 185 TTT GCT GTT CCT ACA AAG TTT ACG CCT AAC TGC CTT AGT GTC TTG GTA 6795

Phe Ala Vai Pro Thr Lys Phe Thr Pro Asa Trp Lea Ser Val Lea Val 190 195 200 GAC AAT TTG CCT GGC ACC AAA GTA AAC GCA GAG AGT GTA GAG AGG ATA 6843Phe Ala Vai Pro Thr Lys Phe Thr Pro Asa Trp Lea Ser Val Lea Val 190 195 200 GAC AAT TTG CCT GCT ACC AAA GTA AAC GCA GAG AGT GTA GAG AGG ATA 6843

Asp "Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val Gia Arg lie 205 210 215 AAA CGG CAA CAC AGC TCA CAA GAA CAG ACT TTC CAG CTG CTG AAG TTA 6891Asp " Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val Gia Arg lie 205 210 215 AAA CGG CAA CAC AGC TCA CAA GAA CAG ACT TTC CAG CTG CTG AAG TTA 6891

Lys Arg Gin His Ser Ser Gln Glu Gla Thr Phe Gin Leu Leu Lys Leu 220 225 230 235 TGG AAA CAT CAA AAC AAA GAC CAA GAT ATA GTC AAG AAG ATC ATC CAA G 6940Lys Arg Gin His Ser Ser Gln Glu Gla Thr Phe Gin Leu Leu Lys Leu 220 225 230 235 TGG AAA CAT CAA AAC AAA GAC CAA GAT ATA GTC AAG AAG ATC ATC CAA G 6940

Trp Lys His Gin Asn Lys Asp Gin Asp lie Val Lys Lys [ le lie G l n 240 245 250 (請先閱讀背面之注意事項再填寫本頁) 訂 d 本紙張尺度適用中國國家標準（CNS ) A4規格（210X 297公釐） 177 3 8 0 7 6 538049 A7 B7 經濟部中央標準局員工消費合作衽印製五、發明説明（178) GTAATTACAT TCCAAAATAC GTCTTTGTAC GATTTTGTAG TATCATCTCT CTCTCTGAGT 7000 TGAACACAAG GCCTCCAGCC ACATTCTTGG TCrtAACTTAC ATTTTCCCTT TCTTGAATCT 7060 TAACCAGCTA AGGCTACTCT CGATGCATTA CTGCTAAAGC TACCACTCAG AATCTCTCAA 7120 AAACTCATCT TCTCACAGAT AACACCTCAA AGCTTGATTT TCTCTCCTTT CACACTGAAA 7180 TCAAATCTTG CCCATAGGCA AAGGGCAGTG TCAAGTTTGC CACTGAGrtTG AAATTAGGAG 7240 AGTCCAAACT GTAGAATTCA CGTTGTGTGT TATTACTTTC ACGAATGTCT GTATTATTAA 7300 CTAAAGTATA TATTGGCAAC TAAGAAGCAA AGTGATATAA ACATGATGAC AAATTAGGCC 7360 AGGCATGGTG GCTTACTCCT ATAATCCCAA CATTTTGGGG GGCCAAGGTA GGCAGATCAC 7420 TTGAGGTCAG GATTTCAAGA CCAGCCTGAC CAACATGGTG AAACCTTGTC TCTACTAAAA 7480 ATACAAAAAT TAGCTGGGCA TGGTAGCAGG CACTTCTAGT ACCAGCTACT CAGGGCTGAG 7540 GCAGGAGAAT CGCTTGAACC CAGGAGATGG AGGTTGCAGT GAGCTGAGAT TGTACCACTG 7600 CACTCCAGTC TGGGCAACAG AGCAAGATTT CATCACACAC ACACACACAC ACACACACAC 7660 ACACATTAGA AATGTGTACT TGGCTTTGTT ACCTATGGTA TTAGTGCATC TATTGCATGG 7720 AACTTCCAAG CTACTCTGGT TGTGTTAAGC TCTTCATTGG GTACrtGGTCA CTAGTATTAA 7730 GTTCAGGTTA TTCGGATGCA TTCCACGGTA GTGATGACAA TTCATCAGGC TAGTGTGTGT 7840 GTTCACCTTG TCACTCCCAC CACTAGACTA ATCTCAGACC TTCACTCAAA GACACATTAC 7900 ACTAAAGATG ATTTGCHTT TTGTGTTTAA TCAAGCAATG GTATAAACCA GCTTGACTCT 7960 CCCCAAACAG TTTTTCGTAC TACAAAGAAG TTTATGAAGC AGAGAAATGT GAATTGATAT 8020 ATATATGAGA TTCTAACCCA GTTCCAGCAT TGTTTCATTG TGTAATTGAA ATCATAGACA 8080 AGCCATTTTA GCCTTTGCTT TCTTATCTAA A A A A A A A A A A AAAAAAATGA AGGAAGGGGT 8140 ATTAAAAGGA GTGATCAAAT TTTAACATTC TCTTTAATTA ATTCATTTTT ΑΑΤΤΤΓΑΟΤΤ 8200 TTTTTCATTT ATTGTGCACT TACTATGTGG TACTGTGCTA TAGAGGCTH AACATTTATA 8260 AAAACACTGT GAAAGTTGCT TCAGATGAAT ATAGGTAGTA GAACGGCAGA ACTAGTATTC 8320 AAAGCCAGGT CTGATGAATC CAAAAACAAA CACCCATTAC TCCCATTTTC TGGGACATAC 8380 TTACTCTACC CAGATGCTCT GGGCTTTGTA ATGCCTATGT AAATAACATA GTTTTATGTT 8440 TGGTTATTTT CCTATGTAAT GTCTACTTAT ATATCTGTAT CTATCTCTTG CTTTGTTTCC 8500 AAAGGTAAAC TATGTGTCTA AATGTGGGCA AAAAATAACA CACTATTCCA AATTACTGTT 8560 CAAATTCCTT TAAGTCAGTG ATAATTATTT GTTTTGACAT TAATCATGAA GTTCCCTGTG 8620 (請先閲讀背面之注意事項再填寫本頁) 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 178 3 8 0 7 6 538049 A7 B7 五、發明説明（179) GGTACTAGGT AAACCTTTAA TAGAATGTTA ATGTTTGTAT TCATTATAAG AATTTTTGGC 8680 TGTTACTTAT TTACAACAAT ATTTCACTCT AATTAGACAT TTACTAAACT TTCTCTTGAA 8740 AACAATGCCC AAAAAAGAAC ATTAGAAGAC ACGTAAGCTC AGTTGGTCTC TGCCACTAAG 8800 ACCAGCCAAC AGAAGCTTGA TTTTATTCAA ACTTTGCATT TTAGCATATT HATCTTGGA 8860 AAATTCAATT GTGTTGGTTT TTTGTTTTTG TTTGTATTGA ATAGACTCTC AGrtrt/UCCArt 8920 TTGTTGAGTA AATCTTCTGG GTTTTCTAAC CTTTCTTTAG AT ATT GAC CTC TGT 8974Trp Lys His Gin Asn Lys Asp Gin Asp lie Val Lys Lys [le lie G ln 240 245 250 (Please read the notes on the back before filling out this page) Order d This paper size applies Chinese National Standard (CNS) A4 specification (210X 297 mm) 177 3 8 0 7 6 538049 A7 B7 Consumption cooperation of employees of the Central Bureau of Standards of the Ministry of Economic Affairs 衽 Printing 5. Invention Description (178) GTAATTACAT TCCAAAATAC GTCTTTGTAC GATTTTGTAG TATCATCTCT CTCTCTGAGA 7000 TGAACACAAG GCCTCCCTAGCT ATCTCTTGG TCrtAACTTAC ATC TACTC ATC BCC AATCTCTCAA 7120 AAACTCATCT TCTCACAGAT AACACCTCAA AGCTTGATTT TCTCTCCTTT CACACTGAAA 7180 TCAAATCTTG CCCATAGGCA AAGGGCAGTG TCAAGTTTGC CACTGAGrtTG AAATTAGGAG 7240 AGTCCAAACT GTAGAATTCA CGTTGTGTGT TATTACTTTC ACGAATGTCT GTATTATTAA 7300 CTAAAGTATA TATTGGCAAC TAAGAAGCAA AGTGATATAA ACATGATGAC AAATTAGGCC 7360 AGGCATGGTG GCTTACTCCT ATAATCCCAA CATTTTGGGG GGCCAAGGTA GGCAGATCAC 7420 TTGAGGTCAG GATTTCAAGA CCAGCCTGAC CAACATGGTG AAACCTTGTC TCTACTAAAA 7480 ATACAAAAAT TAGCTGGGCA TGGTAGCAGG CACTTCTAGT ACCAGCTACT CAGGGCTGAG 7540 GCAGGAGAAT CGCTTGAACC CAGGAGATGG AGGTTGCAGT GAGCTGAGAT TGTACCACTG 7600 CACTCCAGTC TGGGCAACAG AGCAAGATTT CATCACACAC ACACACACAC ACACACACAC 7660 ACACATTAGA AATGTGTACT TGGCTTTGTT ACCTATGGTA TTAGTGCATC TATTGCATGG 7720 AACTTCCAAG CTACTCTGGT TGTGTTAAGC TCTTCATTGG GTACrtGGTCA CTAGTATTAA 7730 GTTCAGGTTA TTCGGATGCA TTCCACGGTA GTGATGACAA TTCATCAGGC TAGTGTGTGT 7840 GTTCACCTTG TCACTCCCAC CACTAGACTA ATCTCAGACC TTCACTCAAA GACACATTAC 7900 ACTAAAGATG ATTTGCHTT TTGTGTTTAA TCAAGCAATG GTATAAACCA GCTTGACTCT 7960 CCCCAAACAG TTTTTCGTAC TACAAAGAAG TTTATGAAGC AGAGAAATGT GAATTGATAT 8020 ATATATGAGA TTCTAACCCA GTTCCAGCAT TGTTTCATTG TGTAATTGAA ATCATAGACA 8080 AGCCATTTTA GCCTTTGCTT TCTTATCTAA AAAAAAAAAA AAAAAAATGA AGGAAGGGGT 8140 ATTAAAAGGA GTGATCAAAT TTTAACATTC TCTTTAATTA ATTCATTTTT ΑΑΤΤΤΓΑΟΤΤ 8200 TTTTTCATTT ATTGTGCACT TACTATGTGG TACTGTGCTA TAGAGGCTH AACATTTATA 8260 AAAACACTGT GAAAGTTGCT TCAGATGAAT ATAGGTAGTA GAACGGCAGA ACTAGTATTC 8320 AAAGCC AGGT CTGATGAATC CAAAAACAAA CACCCATTAC TCCCATTTTC TGGGACATAC 8380 TTACTCTACC CAGATGCTCT GGGCTTTGTA ATGCCTATGT AAATAACATA GTTTTATGTT 8440 TGGTTATTTT CCTATGTAAT GTCTACTTAT ATATCTGTAT CTATCTCTTG CTTTGTTTCC 8500 AAAGGTAAAC TATGTGTCTA AATGTGGGCA AAAAATAACA CACTATTCCA AATTACTGTT 8560 CAAATTCCTT TAAGTCAGTG ATAATTATTT GTTTTGACAT TAATCATGAA GTTCCCTGTG 8620 (Please read the notes on the back of this page and then fill in) this paper Standards are applicable to Chinese National Standards (CNS) A4 specifications (210X297 mm) 178 3 8 0 7 6 538049 A7 B7 V. Description of invention (179) GGTACTAGGT AAACCTTTAA TAGAATGTTA ATGTTTGTAT TCATTATAAG AATTTTTGTCTCAGGCACACATACATAATAACATA TGCCACTAAG 8800 ACCAGCCAAC AGAAGCTTGA TTTTATTCAA ACTTTGCATT TTAGCATATT HATCTTGGA 8860 AAATTCAATT GTGTTGGTTT TTTGTTTTTG TTTGTATTGA ATAGACTCTC AGrtrt / UCCArt 8920 TTGTTGAGTA AATCTTCTGG GTTTTCTA T CTTTCTAG CTTTCTAG

Asp [ le Asp Leu Cys 255 GAA AAC AGC GTG CAG CGG CAC ATT GGA .CAT GCT AAC CTC ACC TTC GAG 9022 GUSer Val Gin Arg His He Gly llis AU Asn Uu Thr Phe Glu 260 265 270 CAG CTT CGT AGC TTG ATG GAA AGC TTA CCG GGA AAG ΑΑΛ GTG GGA GCA 9070Asp [le Asp Leu Cys 255 GAA AAC AGC GTG CAG CGG CAC ATT GGA .CAT GCT AAC CTC ACC TTC GAG 9022 GUSer Val Gin Arg His He Gly llis AU Asn Uu Thr Phe Glu 260 265 270 CAG CTT CGT AGC TTG ATG GAA AGC TTA CCG GGA AAG ΑΑΛ GTG GGA GCA 9070

Gin Leu Arg Ser Leu !1et Glu Ser Leu Pro Gly Lys Lys Val Gly Ala 275 230 285 GAA iAC ATT GAA AAA ACA ATA AAG GCA TGC AAA CCC ACT GAC CAG ATC 9113Gin Leu Arg Ser Leu! 1et Glu Ser Leu Pro Gly Lys Lys Val Gly Ala 275 230 285 GAA iAC ATT GAA AAA ACA ATA AAG GCA TGC AAA CCC ACT GAC CAG ATC 9113

Glu Asp lie Glu lys Thr He Lys Ala Cys Lys Pro Ser Asp Gin [la 290 295 300 經濟部中央標準局員工消費合作社印製 (請先閱讀背面之注意事項再填寫本頁) CTG AAG CTG CTC AGT TTG TGG CGA ATA AAA AAT GGC GAC CAA GAC ACC 9166Glu Asp lie Glu lys Thr He Lys Ala Cys Lys Pro Ser Asp Gin [la 290 295 300 Printed by the Staff Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling this page) CTG AAG CTG CTC AGT TTG TGG CGA ATA AAA AAT GGC GAC CAA GAC ACC 9166

Leu Lys Leu Leu Ser Leu Trp Arg Me Lys Asn Gly Asp Gin Asp Thr 305 310 315 320 TTG AAG GGC CTA ATG CAC GCA CTA AAG CAC TCA AAG ACG TAC CAC TTT 9214Leu Lys Leu Leu Ser Leu Trp Arg Me Lys Asn Gly Asp Gin Asp Thr 305 310 315 320 TTG AAG GGC CTA ATG CAC GCA CTA AAG CAC TCA AAG ACG TAC CAC TTT 9214

Leu Lys Gly Leu Met His Ala Leu Lys His Ser Lys Thr Tyr His Phe 325 330 335 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） 179 3 8 0 7 6 538049 A7 B7 經濟部中央標準局員工消費合作社印製五、發明説明（1 δ ο) CCC AAA ACT GTC ACT CAG ACT CTA AAG AAG ACC ATC AGG TTC CTT CAC 9262 Pro Lys Thr Val Thr Gin Ser Leu Lys Lys Thr [l e Arg Phe Leu His 340 345 350 AGC TTC ACA ATG TAC AAA TTG TAT CAG AAG ΤΤΛ TTT TTA GAA ATG ATA 9310 Ser Phe Thr Me t Tyr lys Leu Tyr Gin Lys Leu Phe Leu Gla Met [le 355 360 365 GGT AAC CAG GTC CAA TCA GTA ΑΑΛ ATA ACC TGC TTA TAACTGGrtrtrt 9356 G 1 y Asn Gin Val Gin Ser Val Lys [le Ser Cys Leu 370 375 330 TGGCCATTGA GCTGTTTCCT CACAATTGGC GAGATCCCAT GGATGAGTAA ACTGTTTCTC 9416 AGGCACTTGA GGCTTTCAGT GATATCTTTC TCATTACCAG TGACTAATTT TGCCACAGGG 9476 TACTAAAAGA AACTATGATG "GGAGAAAGG ACTAACATCT CCTCCAATAA ACCCCAAATG 9536 GTTAATCCAA CTGTCAGATC ：GGATCGTTA TCTACTGACT ATATTTTCCC TTATTACTGC 9596 TTGCAGTAAT TCAACTGGAA ATTAAAAAAA AAAAACTAGA CTCCACTGGG CCTTACTAAA 9656 TATGGGAATG TCTAACTTAA ATAGCTTTGG GATTCCAGCT ATGCTAGAGG CTTTTATTAG 9716 AAAGCCATAT TTTTTTCTGT AAAAGTTACT AATATATCTG TAACACTATT ACAGTATTGC 9776 TATTTATATT CATTCAGATA TAAGATTTGG ACATATTATC ArCCTATAAA GAAACGGTAT 9836 GACTTAATTT TAGAAAGAAA ATTATATTCT GTTTATTATG ACAAATGAAA GAGAAAATAT 9896 ATATTTTTAA TGGAAAGTTT GTAGCATTTT TCTAATAGGT ACTGCCATAT TTTTCTGTGT 9956 GGAGTATTTT ΤΑΤΑΑΠΤΤΑ TCTGTATAAG CTGTAATATC ATTTTATAGA AAATGCATTA 10016 TTTAGTCAAT TGTTTAATGT TGGAAAACAT ATGAAATATA AATTATCTGA ATATTAGATG 10076 CTCTGAGAAA TTGAATGTAC CTTATTTAAA AGATTTTATG GTTTTATAAC TATATAAATG 10136 ACATTATTAA AGTTTTCAAA TTATTTTTTA TTGCTTTCTC TGTTGCTTTT ATTT 10190 (請先閱讀背面之注意事項再填寫本頁)Leu Lys Gly Leu Met His Ala Leu Lys His Ser Lys Thr Tyr His Phe 325 330 335 This paper size applies to Chinese National Standard (CNS) A4 (210X297 mm) 179 3 8 0 7 6 538049 A7 B7 Central Bureau of Standards, Ministry of Economic Affairs Printed by Employee Consumer Cooperatives V. Invention Description (1 δ ο) CCC AAA ACT GTC ACT CAG ACT CTA AAG AAG ACC ATC AGG TTC CTT CAC 9262 Pro Lys Thr Val Thr Gin Ser Leu Lys Lys Thr [le Arg Phe Leu His 340 345 350 AGC TTC ACA ATG TAC AAA TTG TAT CAG AAG ΤΤΛ TTT TTA GAA ATG ATA 9310 Ser Phe Thr Me t Tyr lys Leu Tyr Gin Lys Leu Phe Leu Gla Met [le 355 360 365 GGT AAC CAG GTC CAA TCA GTA ΑΑΛ ATA TACC TTA TAACTGGrtrtrt 9356 G 1 y Asn Gin Val Gin Ser Val Lys [le Ser Cys Leu 370 375 330 TGGCCATTGA GCTGTTTCCT CACAATTGGC GAGATCCCAT GGATGAGTAA ACTGTTTCTC 9416 AGGCACTTGA GGCTTTCAGT GATATCTTTC TCATTACCAG TGACTAATTT TGCCACAGGG 9476 TACTAAAAGA AACTATGATG " GGAGAAAGG ACTAACATCT CCTCCAATAA ACCCCAAATG 9536 GTTAATCCAA CTGTCAGATC: GGATCGTTA TCT ACTGACT ATATTTTCCC TTATTACTGC 9596 TTGCAGTAAT TCAACTGGAA ATTAAAAAAA AAAAACTAGA CTCCACTGGG CCTTACTAAA 9656 TATGGGAATG TCTAACTTAA ATAGCTTTGG GATTCCAGCT ATGCTAGAGG CTTTTATTAG 9716 AAAGCCATAT TTTTTTCTGT AAAAGTTACT AATATATCTG TAACACTATT ACAGTATTGC 9776 TATTTATATT CATTCAGATA TAAGATTTGG ACATATTATC ArCCTATAAA GAAACGGTAT 9836 GACTTAATTT TAGAAAGAAA ATTATATTCT GTTTATTATG ACAAATGAAA GAGAAAATAT 9896 ATATTTTTAA TGGAAAGTTT GTAGCATTTT TCTAATAGGT ACTGCCATAT TTTTCTGTGT 9956 GGAGTATTTT ΤΑΤΑΑΠΤΤΑ TCTGTATAAG CTGTAATATC ATTTTATAGA AAATGCATTA 10016 TTTAGTCAAT TGTTTAATGT TGGAAAACAT ATGAAATATA AATTATCTGA ATATTAGATG 10076 CTCTGAGAAA TTGAATGTAC CTTATTTAAA AGATTTTATG GTTTTATAAC TATATAAATG 10136 ACATTATTAA AGTTTTCAAA TTATTTTTTTT TTGC TTGC TTGC

、1T d 本紙張尺度適用中國國家標準（CNS ) Α4規格（210X297公釐） ! g〇 3 8 0 7 6、 1T d This paper size is applicable to China National Standard (CNS) Α4 specification (210X297 mm)! G〇 3 8 0 7 6

Claims

538049 Outline 4?

Supplementary Patent No. 85108022 Patent Application Amendment of Patent Scope This announcement is printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs— (June 4, 91), a protein produced by human fibroblasts that inhibits human osteoclast formation The N-terminal sequence of this protein is the protein shown in the following amino acid sequence ... Gl ^ Thr Phe Pro Pro Lys Tyr Leu His Tyr Asp Glu GIu Thr Ser 1 5 l 015 It is characterized by the following physical and chemical properties, At the same time, the inhibition test of osteoclast formation was performed by using rat bone marrow cells as target cells in the coexistence of activated vitamin h (calcified glycol) in the presence of activated vitamin h (calcified glycol). Osteoblast differentiation and / or maturation inhibitory activity: ⑷ Molecular weight (according to SDS-APGE): about 60kD (under reducing conditions), about 60kD and about 120kD (under non-reducing conditions); (b) affinity: for cation exchangers Has affinity with heparin; (c) Thermal stability: at 70. (: 10 minutes or 56χ: 30 minutes of heat treatment, its osteoclast differentiation and maturation inhibitory activity will be reduced. Under 90 ° C 10 minutes of heat treatment, osteoclast differentiation and maturation inhibitory activity will disappear … (D) Amino acid sequence: It has the following amino acid sequence as its internal amino acid sequence: Zaa Tyr His Phe Pro Lys 1 5 Zaa Gin His Ser Zaa Gin Glu Gin Thr Phe Gin T γ This paper size is applicable China National Standard (CNS) A4 (210 x 297 mm) ^-土 —yS ··-1

38076 538049 --------- Η3 1 5 10 lie Arg Phe Leu His Ser Phe Thr Met Tyr Lys 1 5 10. 2. A method for producing a protein that inhibits human osteoclast formation as described in item i of the patent application, which is characterized by culturing human fibroblasts', passing the culture solution through a heparin separation tube, and using 1 m containing 2 m NaC1. mM TdS-HCl buffer solution (pH 7 勹), and the heparin-adsorbing crescent cell formation inhibitory factor component was obtained, and this component was added to 卩, anion 乂 was replaced in a separation tube, the non-adsorbed components were pooled, and heparin was first separated The tube 2 is based on Seba Gurung blue pigment separation tube, and then purified by reverse phase separation tube adsorption and dissolution treatment. The method of manufacturing the protein shellfish that inhibits the formation of human osteoclasts in the second item of the patent \ 'its system An alumina ceramic sheet is used as a carrier for cell culture. A protein that inhibits the formation of human osteoclasts, which is characterized by the following amino acid sequence: The A4 specification printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs (210 X 297 mm) This paper is applicable to 38076 538049 H3 Glu Thr Phe Pro Pro Lys T printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs yr Leu His Tyr Asp Glu Glu Thr Ser 15 10 15 His Gin Leu Leu Cys Asp Lys Cys Pro Pro Gly Thr Tyr Leu Lys 20 25 30, Gin His Cys Thr Ala Lys Trp Lys Thr Val Cys Ala Pro Cys Pro 35 40 45 Asp His Tyr Tyr Thr Asp Ser Trp His Thr Ser Asp Glu Cys Leu 50 55 60 Tyr Cys Ser Pro Val Cys Lys Glu Leu Gin Tyr Val Lys Gin Glu 65 70 75 Cys Asn Arg Thr His Asn Arg Val Cys Glu Cys Lys Glu Gly Arg 80 85 90 Tyr Leu Glu lie Glu Phe Cys Leu Lys His Arg Ser Cys Pro Pro 95 100 105 Gly Phe Gly Val Val Gin Ala Gly Thr Pro Glu Arg Asn Thr Val 110 115 120 Cys Lys Arg Cys Pro Asp Gly Phe Phe Ser Asn Glu Thr Ser Ser 125 130 135 Lys Ala Pro Cys Arg Lys His Thr Asn Cys Ser Val Phe Gly Leu 140 145 150 Leu Leu Thr Gin Lys Gly Asn Ala Thr His Asp Asn lie Cys Ser 155 160 165 Standard (CNS) A4 size (210 x 297 mm) 38076 538049 H3 Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs Gly Asn Ser Glu Ser Thr Gin Lys Cys Gly lie Asp Val Thr Leu 170 175 180 Cys Glu Glu Ala Phe Ph e Arg Phe Ala Val Pro Thr Lys Phe Thr 185 190 195 Pro Asn Trp Leu Ser Val Leu Val Asp Asn Leu Pro Gly Thr Lys 200 205 210 Val Asn Ala Glu Ser Val Glu Arg lie Lys Arg Gin His Ser Ser 215 220 225 Gin Glu Gin Thr Phe Gin Leu Leu Lys Leu Trp Lys His Gin Asn 230 235 240 Lys Asp Gin Asp lie Val Lys Lys lie lie Gin Asp lie Asp Leu 245 250 255 Cys Glu Asn Ser Val Gin Arg His lie Gly His Ala Asn Leu Thr 260 265 270 Phe Glu Gin Leu Arg Ser Leu Met Glu Ser Leu Pro Gly Lys Lys 275 280 285 Val Gly Ala Glu Asp lie Glu Lys Thr lie Lys Ala Cys Lys Pro 290 295 300 Ser Asp Gin lie Leu Lys Leu Leu Ser Leu Trp Arg lie Lys Asn 305 310 315 Gly Asp Gin Asp Thr Leu Lys Gly Leu Met His Ala Leu Lys His 320 325 330 Ser Lys Thr Tyr His Phe Pro Lys Thr Val Thr Gin Ser Leu Lys 335 340 345 Lys Thr lie Arg Phe Leu His Ser Phe Thr Met Tyr Lys Leu Tyr 350 355 360 Gin Lys Leu Phe Leu Glu Met lie Gly Asn Gin Val Gin Ser Val 365 370 375 Lys He Ser Cys Leu 380 0 ··, a kind of cDNA, which encodes the fourth item in the scope of patent applications Place Amino acids suitable for the present paper China National Standard Scale (CNS) A4 size (210 X 297 mm); 4 38076 538049 H3 by inhibition of protein sequences of human osteoclast formation. 6. — A cDNA encoding a precursor of a protein that inhibits human osteoclast formation in the fourth patent application. The amino acid sequence of the precursor is described in sequence number 5 in the sequence listing, and the fluorenyl sequence of the cDNA is as shown by: employee benefits Committee of the central Bureau of standards, Ministry of economic Affairs printed ATGAACAACT CAGGAAACGT TGTGACAAAT GTGTGCGCCC CTATACTGCA CACAACCGCG CATAGGAGCT GTTTGCAAAA AGAAAACACA CACGACAACA CTGTGTGAGG AGTGTCTTGG AAACGGCAAC AACAAAGACC GTGCAGCGGC AGCTTACCGG CCCAGTGACC ACCTTGAAGG GTCACTCAGA TATCAGAAGT TTATAA TGCTGTGCTG TTCCTCCAAA GTCCTCCTGG CTTGCCCTGA GCCCCGTGTG TGTGCGAATG GCCCTCCTGG GATGTCCAGA CAAATTGCAG TATGTTCCGG AGGCATTCTT CGCGCTCGTG GTACCTTCAT TACCTACCTA CCACTACTAC CAAGGAGCTG CAAGGAAGGG ATTTGGAGTG TGGGTTCTTC TGTCTTTGGT AAACAGTGAA CAGGTTTGCT TTTCTGGACA TATGACGAAG AAACAACACT ACAGACAGCT CAGTACGTCA CGCTACCTTG GTGCAAGCTG TCAAATGAGA CTCCTGCTAA TCAACTCAAA GTTCCTACAA TCTCCATTAA AAACCTCTCA GTACAGCAAA GGCACACCAG AGCAGGAGTG AGATAGAGTT GAACCCCAGA CGTCATCTAA CTCAGAAAGG AATGTGGAAT AGTTTACGCC GTGGAC CACC 60 TCAGCTGTTG 120 GTGGAAGACC 180 TGACGAGTGT 240 CAATCGCACC 300 CTGCTTGAAA 360 GCGAAATACA 420 AGCACCCTGT 480 AAATGCAACA 540 AGATGTTACC 600 TAACTGGCTT 660 TAGACAATTT ACAGCTCACA AAGATATAGT ACATTGGACA GAAAGAAAGT AGATCCTGAA GCCTAATGCA GTCTAAAGAA TATTTTTAGA GCCTGGCACC AGAACAGACT CAAGAAGATC TGCTAACCTC GGGAGCAGAA GCTGCTCAGT CGCACTAAAG GACCATCAGG AATGATAGGT AAAGTAAACG TTCCAGCTGC ATCCAAGATA ACCTTCGAGC GACATTGAAA TTGTGGCGAA CACTCAAAGA TTCCTTCACA AACCAGGTCC CAGAGAGTGT TGAAGTTATG TTGACCTCTG AGCTTCGTAG AAACAATAAA TAAAAAATGG CGTACCACTT GCTTCACAAT AATCAGTAAA AGAGAGGATA 720 GAAACATCAA 780 TGAAAACAGC 840 CTTGATGGAA 900 GGCATGCAAA 960 CGACCAAGAC 1020 TCCCAAAACT 1080 GTACAAAGCT 1GCATA 1TBATA It is composed of amino acids Nos. 1 to 380, and obtained from the cDNA expression of item 6 in the scope of patent application. This paper is applicable to China National Standard (CNS) A4 specifications (210, 297 mm) 38076 538049 H3 gets 0 Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser • 20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 -11 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35 Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80 Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Leu Lys 85 90 95 His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Gly Thr 100 105 110 Printed by the Staff Welfare Committee of the Central Bureau of Standards of the Ministry of Economic Affairs This paper is sized for the Chinese National Standard (CNS) A4 (210 x 297 mm) 38076 538049 H3 Printed by Pro Glu Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 115 120 125 Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 130 135 140 Cys Ser Val Phe Gly Leu Leu Lea Thr Gin Lys Gly Asn Ala Thr 145 150 155 His Asp Asn lie Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Cys 160 165 170 Gly lie Asp Val Thr Leu Cys Glu Glu Ala Phe Phe Arg Phe Ala 175 180 185 Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val Leu Val Asp 190 195 200 Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg lie 205 210 215 Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe Gin Leu Leu Lys 220 225 230 Leu Trp Lys His Gin Asn Lys Asp Gin Asp lie Val Lys Lys lie 235 240 245 lie Gin Asp lie Asp Leu Cys Glu Asn Ser Val Gin Arg His lie 250 255 260 Gly His Ala Asn Leu Thr Phe Glu Gin Leu Arg Ser Leu Met Glu 265 270 275 Ser Leu Pro Gly Lys Lys Val Gly Ala Glu Asp lie Glu Lys Thr 280 285 290 lie Lys Ala Cys Lys Pro Ser Asp Gin lie Leu Lys Leu Leu Ser 295 300 305 Leu Trp Arg lie Lys Asn Gly Asp Gin Asp Thr Leu Lys Gly Leu 310 315 320 This paper size applies to Chinese National Standard (CNS) A4 (210 x 297 cm) ^ 7 38076 538049 H3 Met His Ala Leu Lv ^ crfy Hxs Ser Lys Thr Ty r His Phe Pro Lys Thr 325 330 335 Gin Ser Leu Lys Lys Thr lie Arg Phe Leu His Ser Phe 340 345 350 Thr Met Tyr Lys Leu Tyr Gin Lys Leu Phe Leu Glu Met lie Gly 355 360 365 Asn Gin Val Gin Ser Val Lys He Ser Cys Leu 370 375 380 o 8. —A method for producing a protein with the following physicochemical properties and osteoclast differentiation and / or maturation inhibitory activity by genetic engineering, which is characterized by inserting a CDNA encoding a protein amino acid sequence of a patent application No. 4 into a vector Into plastids, and then introduce the plastids into cells or strains of host cells for culture. Pass the culture solution, pass the solution through a heparin separation tube, and wash with a linear gradient solution of U2MNaa to collect osteoclast formation. Components that inhibit activity and obtain the non-adsorbed component by affinity chromatography: "(a) Molecular weight (according to SDS-PAGE): about 60kD (under reducing conditions), about 60kD and about 120kD (non-reducing conditions) Bottom); Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs (b) Affinity: has affinity with cation exchangers and heparin; (c) Thermal stability: borrow 7 (TC 10 minutes or 56.30 minutes) Heat treatment will reduce the differentiation and maturation inhibitory activity of osteoclasts, and heating treatment at ° C for 10 minutes will make the osteoclasts scoring and maturation inhibition activity disappear; (d) Amine group Acid sequence: Those who have the following amino acid sequence as the internal amino acid sequence: Zaa Tyr His Phe Pro Lys This paper size applies to China National Standard (CNS) A4 specifications (210 x ~ 297 mm y 38076 538049- -----_ H3 __ 1 5 Zaa Gin His Ser Zaa Gin Glu Gin Thr Phe Gin Leu Zaa Lys 1 5 10 Zaa lie Arg Phe Leu His Ser Phe Thr Met Tyr Lys 1 5 10 (e) Amino acid sequence: Those with the following amino acid sequences as the n-terminal amino acid sequence: Glu Thr Phe Pro Pro Lys Tyr Leu His Tyr Asp Giu Glu Thr Ser 1 5 10 15 o 9 A method for a protein having osteoclast differentiation and / or maturation inhibitory activity, which is characterized in that mammalian cells are used as host cells. 10. If the osteoclasts are manufactured by genetic engineering, such as in item 9 of the patent application scope, Method for differentiation and / or maturation-inhibitory protein, in which the host cell is 293 / EBNA cells or CHO cells. 11 · A cDNA encoding a protein that inhibits osteoclast formation, which is the cDNA shown in the following amyloid sequence: Central Ministry of Economic Affairs Associate Bureau employee benefits committee print 38,076 sheets scale applicable Chinese national 297 ^) " 538049 H3 ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT CTATACTGCA GCCCCGTGTG CAAGGAGTGC AATCGCACCC AAGGAAGGGC GCTACCTTGA GATAGAGTTC TGCTTGAAAC TTTGGAGTGG TGCAAGCTGG AACCCCAGAG CGAAATACAG GGGTTCTTCT CAAATGAGAC GTCATCTAAA GCACCCTGTA GTCTTTGGTC TCCTGCTSAC TCAGAAAGGA AATGCAACAC AACAGTGAAT CAACTCAAAA ATGTGGAATA GATGTTACCC AGGTTTGCTG TTCCTACAAA GTTTACGCCT AACTGGCTTA CCTGGCACCA AAGTAAACGC AGAGAGTGTA GAG4GGATAA GAACAGACTT TCCAGCTGCT GAAGTTATGG AAACATCAAA AAGAAGATCA TCCAAGATAT TGACCTCTGT GAAAACAGCG GCTAACCTCA CCTTCGAGCA GCTTCGTAGC TTGATGGAAA GGAGCAGAAG ACATTGAAAft AACAATAAAG GCATGCAAAC CTGCTCAGTT TGTGGCGAAT AAAAAATGGC GACCAAGACA GCACTAAAGC ACTCAAAGAC GTACCACTTT CCCAAAACTG ACCATCAGGT TCCTTCACAG CTTCACAATG TACAAATTGT ATGATAGGTA ACCAGGTCCA ATCAGTAAAA ATAAGCTGCT Central Standard of the Ministry of Economic Affairs Bureau of Employee Benefits Committee printed TCTCCATTAA GTGGACCACC 60 AAACCTCTCA TCAGCTGTTG 120 GTACAGCAAA GTGGAAGACC 180 GGCACACCAG TGACGAGTGT. 240 ACAACCGCGT GTGCGAATGC 300 ATAGGAGCTG CCCTCCTGGA 360 TTTGCAAAAG ATGTCCAGAT 420 GAAAACACAC AAATTGCAGT 480 ACGACAACAT ATGTTCCGGA 540 TGTGTGAGGA GGCATTQTTC 600 GTGTCTTGGT AGACAATTTG 660 AACGGCAACA CAGCTCACAA 720 ACAAAGACCA AGATATAGTC 780 TGCAGCGGCA CATTGGACAT 840 GCTTACCGGG AAAGAAAGTG 900 CCAGTGACCA GATCCTGAAG 960 CCTTGAAGGG CCTAATGCAC 1020 TCACTCAGAG TCTAAAGAAG 1080 ATCAGAAGTT ATTTTTAGAA 1140 TATAA 1185 12. —A kind of protein that inhibits osteoclast formation and is composed of the following amino acid sequences Nos. 1 to 373, which are obtained from the cDNA expression of the 11th scope of the patent application: This paper size applies Chinese national standards (CNS ) A4 size (210 X 297 public love) 10 380 ^ 6 538049 H3 Printed by Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 1 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35 Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Gla Cys 55 60 65 Asn Arg Thr His Asn Arg Val Cys Glu Cys Lys Glu Gly Arg Tyr 70 75 80 Leu Glu lie Glu Phe Cys Leu Lys His Arg Ser Cys Pro Pro Gly 85 90 95 Phe Gly Val Val Gin Ala Gly Thr Pro Glu Arg Asn Thr Val Cys 100 105 110 Lys Arg Cys Pro Asp Gly Phe Phe Ser Asn Glu Thr Ser Ser Lys 115 120 125 Ala Pro Cys Arg Lys His Thr Asn Cys Ser Val Phe Gly Leu Leu 130 135 140 Leu Thr Gin Lys Gly Asn Ala Thr His Asp Asn lie Cys Ser Gly 145 150 155 Asn Ser Glu Ser Thr Gin Lys Cys Gly lie Asp Val Thr Leu Cys 160 165 170 Glu Glu Ala Phe Phe Arg Phe Ala Val Pro Thr Lys Phe Thr Pro 175 180 185 This paper size applies the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 11 38076 538049 H3 Ministry of Economy Printed by the Standards Bureau Staff Welfare Committee Asn Trp Leu Ser Val Leu Val Asp Asn Leu Pro Gly Thr Lys Val 190 195 200 Asn Ala Glu Ser Val Glu Arg lie Lys Arg Gin His Ser Ser Gin 205 210 215 Glu Gin Thr Phe Gin Leu Leu Lys Leu Trp Lys His Gin Asn Lys 220 225 230 Asp Gin Asp lie Val Lys Lys lie lie Gin Asp lie Asp Leu Cys 235 240 245 Glu Asn Ser Val Gin Arg His lie Gly His Ala Asn Leu Thr Phe 250 255 260 Glu Gin Leu Arg Ser Leu Met Glu Ser Leu Pro Gly Lys Lys Val 265 270 275 Gly Ala Glu Asp lie Glu Lys Thr lie Lys Ala Cys Lys Pro Ser 280 285 290 Asp Gin lie Leu Lys Leu Leu Ser Leu Trp A rg He Lys Asn Gly 295 300 305 Asp Gin Asp Thr Leu Lys Gly Leu Met His Ala Leu Lys His Ser 310 315 32〇Lys Thr Tyr His Phe Pro Lys Thr Val Thr Gin Ser Leu Lys Lys 325 330 335 Thr lie Arg Phe Lea His Ser Phe Thr Met Ty ^ Lys Leu Tyr Gln 340 345 35〇Lys Leu Phe Leu Glu Met lie Gly Asn Gin Val Gln Ser Val L ^ s 355 360 365 lie Ser Cys Leu 370. 1 3 · —A cDNA encoding a protein that inhibits osteoclast formation 'is characterized by encoding the following amino acid sequence: __ This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 12 38076 538049 H3 Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economy Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser • 20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 1 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35 Val Cys Ala Pro Cys Pro flsp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Cys 55 60 65 Asn Arg Thr His Asn Arg Val Cys Glu Cys Lys Glu Gly Arg Tyr 70 75 80 Leu Glu lie Glu Phe Cys Leu Lys His Arg Ser Cys Pro Pro Gly 85 90 95 Phe Gly Val Val Gin Ala Gly Thr Pro Glu Arg Asn Thr Val Cys 100 105 110 Lys Arg Cys Pro Asp Gly Phe Phe Ser Asn Glu Thr Ser Ser Lys 115 120 125 Ala Pro Cys Arg Lys His Thr Asn Cys Ser Val Phe Gly Leu Leu 130 135 140 Leu Thr Gin Lys Gly Asn Ala Thr His Asp Asn lie Cys Ser Gly 145 150 155 Asn Ser Glu Ser Thr Gin Lys Cys Gly lie Asp Val Thr Leu Cys 160 165 170 Glu Glu Ala Phe Phe Arg Phe Ala Val Pro Thr Lys Phe Thr Pro 175 180 185 This paper size applies to Chinese National Standard (CNS) A4 (210 X 297 mm) 13 38076 538049 Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs H3_ Asn Trp Leu Ser Val Leu Val Asp Asn Leu Pro Gly Thr Lys Val 190 195 200 Asn Ala Glu Ser Val Glu Arg lie Lys Arg Gin His Ser Ser Gin 205 210 215 Glu Gin Thr Phe Gin Leu Leu Lys Leu Trp Lys His Gin Asn Lys 220 225 230 Asp Gin Asp lie Val Lys Lys lie lie Gin Asp lie Asp Leu Cys 235 240 245 Glu Asn Ser Val Gin Arg His lie Gly His Ala Asn Leu Thr Phe 250 255 260 Glu Gin Leu Arg Ser Leu Met Glu Ser Leu Pro Gly Lys Lys Val 265 270 275 Gly Ala Glu Asp lie Glu Lys Thr lie Lys Ala Cys Lys Pro Ser 280 285 290 Asp Gin lie Leu Lys Leu Leu Ser Leu Trp Arg lie Lys Asn Gly 295 300 305 Asp Gin Asp T hr Leu Lys Gly Leu Met His Ala Leu Lys His Ser 310 315 320 Lys Thr Tyr His Phe Pro Lys Thr Val Thr Gin Ser Leu Lys Lys 325 330 335 Thr lie Arg Phe Leu His Ser Phe Thr Met Tyr Lys Leu Tyr Gin 340 345 350 Lys Leu Phe Leu Glu Met lie Gly Asn Gin Val Gin Ser Val Lys 355 360 365 lie Ser Cys Leu 370. 14. A cDNA encoding a protein that inhibits the formation of osteoclasts, which is the cDNA shown in the following 塩 -based sequence: This paper size applies to Chinese national standard 丨 (CNS) A4 size (210 X 297 mm) 14 38076 538049 H3 ATGAACAAGT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 GTTTGCAAAA GATGTCCAGA TGGGTTCTTC TCAAATGAGA CGTCATCTAA AGCACCCTGT 480 AGAAAACftCA CAAATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG AAATGCAACA 540 CACGACAACA TATGTTCCGG AAACAGTGAA TCAACTCAAA AATGTGGAAT AGATGTTACC 600 CTGTGTGAGG AGGCATTCTT CAGGTTTGCT GTTCCTACAA AGTTTTCGCC TAGGGGTA TAGGC CACC AAAGTAAACG CAGAGAGTGT AGAGAGGATA 720 AAACGGCAAC ACAGCTCACA AGAACAGACT TTCCAGCTGC TGAAGTTATG GAAACATCAA 780 AACAAAGACC AAGATATAGT CAAGAAGATC ATCCAAGATA TTGACCTCTG TGAAAACAGC 840 GTGCAGCGGC ACATTGGACA TGCTAACCTC AGTTTGTGGC GAATAAAAAA TGGCGACCAA 900 GACACCTTGA AGGGCCTAAT GCACGCACTA AAGCACTCAA AGACGTACCA CTTTCCCAAA 960 ACTGTCACTC AGAGTCTAAA GAAGACCATC AGGTTCCTTC ACAGCTTCAC AATGTACAAA 1020 TTGTATCAGA AGTTATTTTT AGAAATGATA GGTAACCAGG TCCAATCAGT AAAAATAAGC 1080 TGCTTATAA 1089 square 1 5. -A protein that inhibits human osteoclast formation and is composed of the following amino acid sequences Nos. 1 to 341, which are obtained from the expression of cDNA in item 14 of the patent application scope: Member of the Central Standards Bureau, Ministry of Economic Affairs, Welfare Committee The paper size for printing is applicable to China National Standard (CNS) A4 (丨 210 X 297 mm) 15 38076 538049 H3 Met Asn Lys Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 —15 -10 lie Lys Trp Thr Thr Gla Glu Thr Phe Pro Pro Lys Tyr Leu His -5 1 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35 Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80 Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Gla Phe Cys Leu Lys 85 90 95 His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala. Gly Thr 100 105 110 Pro Glu Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 115 120 125 Printed by the Staff Welfare Committee of the Central Bureau of Standards of the Ministry of Economic Affairs This paper is in accordance with China National Standard (CNS) A4 (210 X 297) 16 38076 538049 H3 Printed by the Employee Welfare Committee of the Central Standards Bureau of the Ministry of Economy Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys Arg lys His Thr Asn 130 135 140 Cys Ser Val Phe Gly Leu Leu Lea Thr Gin Lys Gly Asn Ala Thr 145 150 155 His Asp Asn lie Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Cys 160 165 170 Gly lie Asp Val Thr Leu Cys Glu Glu Ala Phe Phe Arg Phe Ala 175 180 185 Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val Leu Val Asp 190 195 200 Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg lie 205 210 215 Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe Gin Leu Leu Lys 220 225 230 Leu Trp Lys His Gin Asn Lys Asp Gin Asp lie Val Lys Lys lie 235 240 245 lie Gin Asp lie Asp Leu Cys Glu Asn Ser Val Gin Arg His lie 250 255 260 Gly His Ala Asn Leu Ser Leu Trp Arg lie Lys Asn Gly Asp Gin 265 270 275 Asp Thr Leu Lys Gly Leu Met His Ala Leu Lys His Ser Lys Thr 280 285 290 Tyr His Phe Pro Lys Thr Val Thr Gin Ser Leu Lys Lys Thr lie 295 300 305 Arg Phe Leu His Ser Phe Thr Met Tyr Lys Leu Tyr Gin Lys Leu 310 315 320 Phe Leu Glu Met lie Gly Asn Gin Val Gin Ser Val Lys lie Ser 325 330 335 Cys Leu 340 〇16 · —a cdNA encoding a protein that inhibits osteoclast formation, its characteristics paper Standards are in accordance with Chinese National Standard (CNS) A4 specifications (210 X 297 mm), 17 38076 538049 H3 are those encoding the following amino acid sequences: Met Asn Lys Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 1 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35 Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn A rg Val Cys 70 75 80 Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Leu Lys 85 90 95 His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala. Gly Thr 100 105 ， 110 Pro Glu Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs 20 This paper size applies to the Chinese National Standard (CNS) A4 (210 X 297 mm) ) 18 38076 538049 H3 Printed by the Employee Welfare Committee of the Central Standards Bureau of the Ministry of Economy Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 130 135 140 Cys Ser Val Phe Gly Leu Leu Leu Thr Gin Lys Gly Asn Ala Thr 145 150 155 His Asp Asn lie Cys Ser Gly Asn Ser Gla Ser Thr Gin Lys Cys 160 165 170 Gly lie Asp Val Thr Leu Cys Glu Glu Ala Phe Phe Arg Phe Ala 175 180 185 Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val Leu Val Asp 190 195 200 Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg lie 205 210 215 Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe Gin Leu Leu Lys 220 225 230 Leu Trp Lys His Gin Asn Lys Asp Gin Asp lie Val Lys Lys lie 235 240 245 lie Gin Asp lie Asp Leu Cys Glu Asn Ser Val Gin Arg His lie 250 255 260 Gly His Ala Asn Leu Ser Leu Trp Arg lie Lys Asn Gly Asp Gin 265 27Q 275 Asp Thr Leu Lys Gly Leu Met His Ala Leu Lys His Ser Lys Thr 280 285 290 Tyr His Phe Pro Lys Thr Val Thr Gin Ser Leu Lys Lys Thr lie 295 300 305 Arg Phe Leu His Ser Phe Thr Met Tyr Lys Leu Tyr Gin Lys Leu 310 315 320 Phe Leu Glu Met lie Gly Asn Gin Val Gin Ser Val Lys lie Ser 325 330 335 Cys Leu 340 1 7-A cDNA encoding a protein that inhibits osteoclast formation, its characteristics in paper size Applicable to China National Standard (CNS) A4 specification (210 X 297 mm) 19 38076 538049 H3 is the cDNA shown in the following fluorene-based sequence: ATGAACAAGT TGCTGTGCTG CTCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCGCGCTCTCTCTCACTCAGTCACTCAGTCAC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 CATAGGAGGCGCGCGC GTACGTGTCA ATGTGCAGCA 420 AAATTAATTA GGATCATGCA AAGTCAGATA GTTGTGACAG TTTAG 465. 1 8 · A protein that inhibits human osteoclast formation and is composed of the following amino acid sequences Nos. 1 to 133, which are obtained from the cDNA expression of item 17 of the scope of patent application: Central Bureau of Standards, Ministry of Economic Affairs Printed by the Employee Welfare Committee. The paper size applies to the China National Standard for Housing (CNS) A4 (21〇i 297 mm) 20 08076 538049 H3 Printed by the Employee Welfare Committee of the Central Standards Bureau of the Ministry of Economy Met Asn Lys Leu Leu Cys Cys Ser Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 1 5 Tyr Asp Glu Glu Thr Ser His Gin Lea Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35 Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80 Gla Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Leu Lys 85 90 95 His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Gly Thr 100 105 110 Cys Gin Cys Ala Ala Lys Leu lie Arg lie Met Gin Ser Gin lie 115 120 125 Val Val Thr Val 130. 19. · A cdNA encoding a protein that inhibits the formation of osteoclasts, which is characterized by encoding the following amino acid sequence: This paper size applies to Chinese National Standard (CNS) A4 (210 X 297 mm) 21 38076 538049 H3 Ministry of Economic Affairs Met Asn Lys Leu Leu Cys Cys Ser Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 1 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Fro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35 Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80 Glu Cys Lys Glu Gly Arg Tyr Leu Glu Glu Glu Phe Cys Leu Lys 85 90 95 His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Gly Thr 100 105 110 Cys Gin Cys Ala Ala Lys Leu lie Arg lie Met Gin Ser Gin lie 115 120 125 Val Val Thr Val 130 o 2 0 . —A cdNA encoding a protein that inhibits osteoclast formation, which is characterized by the following cDNA sequence shown in the following 塩 -based sequence: · This paper size applies Chinese National Standard (CNS) A4 specification (210 X 297 mm) 22 38076 538049 H3 ATGAACAAGT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTC4 AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GATGCAGGAG AAGACCCAAG 420 CCACAGATAT GTATCTGA 438. twenty one . —A protein that inhibits human osteoclast formation and consists of the following amino acid sequences Nos. 1 to 124, which is obtained from the cDNA expression of the 20th patent application: Met Asn Lys Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 1 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35 Printed by the Staff Welfare Committee of the Central Bureau of Standards of the Ministry of Economic Affairs This paper applies Chinese National Standard (CNS) A4 (210 X 297 mm) 23 38076 I 538049 H3 Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80 Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Leu Lys 85 90 95 His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Gly Cys 100 105 110 Arg Arg Arg Pro Lys Pro Gin lie Cys lie 115 120 125 Printed by the Staff Welfare Committee of Zhongli Standards Bureau, Ministry of Economic Affairs 22. —A cDNA encoding a protein that inhibits osteoclast formation. It encodes the following amino acid sequences: Met Asn Lys Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 1 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35 paper Standards are applicable to China National Standard (CNS) A4 specifications 丨 (210 x 297 mm) 24 38076 538049 H3 Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80 Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Leu Lys 85 90 95 His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Gly Cys 100 105 110 Arg Arg Arg Pro Lys Pro Gin lie Cys lie 115 120 125. twenty three. - encodings inhibition cDNA-protein formation of osteoclasts, wherein the cDNA shown below Salt yl sequence: ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA. GCGAAATACA 420 GTTTGCAAAA GATGTCCAGA TGGGTTCTTC TCAAATGAGA CGTCATCTAA AGCACCCTGT 480 AGAAAACACA CAAATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG AAATGCAACA 540 CACGACAACA TATGTTCCGG AAACAGTGAA TCAACTCAAA AATGTGGAAT AGATGTTACC 600 CTGTGTGAGG AGGCATTCTT CAGGTTTGCT GTTCCTACAA AGTTTACGCC TAACTGGCTT 660 Ben paper scale applicable to Chinese National Standard (CNS) Μ specifications ⑽X 297 male% ^ 38076 538049 ___H3_ AGTGTCTTGG TAGACAATTT GCCTGGCACC AAAGTAAACG CAGAGAGTGT AGAGAGGATA 720 AAACGGCAAC ACAGCTCACA AGAACAGACT TTCCAGCTGC TGAAGTTATG GAAACATCAA 780 AACAAAGACC AAGATATAGT CAAGAAGATC ATCCAAGATA TTGACCTCTG TGAAAACAGC 840 GTGCAGCGGC ACATTGGACA TGCTAACCTC ACCTTCGAGC AGCTTCGTAG CTTGATGGAA 900 AGCTTACCGG GAAAGAAAGT GGGAGCAGAA GACATTGAAA AAACAATAAA GGCATGCAAA 960 CCCAGTGACC AGATCCTGAA GCTGCTCAGT TTGTGGCGAA TAAAAAATGG CGACCAAGAC 1020 ACCTTGAAGG GCCTAATGCA CGCACTAAAG CACTCAAAGA CGTACCACTT TCCCAAAACT 1080 GTCACTCAGA GTCTAAAGAA GACCATCAGG TTCCTTCACA GCTTCACAAT GTACAAATTG 1140 TATCAGAAGT TATTTTTAGA AATGATAGGT AACCAGGTCC AATCA GTAAA AATAAGCTGC 1200 TTATAA 1206 D2 4. —A protein that inhibits osteoclast formation and is composed of the following amino acid sequences Nos. 1 to 380, which are obtained from the cDNA expression of the 23rd scope of the patent application: Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs The paper size of the paper is in accordance with China National Standard (CNS) A4 (210 X 297 mm) 26 38076 538049 H3 Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 _1 1 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35 Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80 Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Leu Lys 85 90 95 His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala G-ly Thr 100 105 110 Pro Glu Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 115 120 125 Printed by the Staff Welfare Committee of the Central Bureau of Standards of the Ministry of Economic Affairs. The paper size applies to the Chinese National Standard (CNS) A4 (210 X 297 mm) 538049 H3 Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 130 135 140 Cys Ser Val Phe Gly Leu Leu Leu Thr Gin Lys Gly Asn Ala Thr 145 150 155 His Asp Asn lie Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Ser 160 165 170 Gly lie Asp Val Thr Leu Cys Glu Glu Ala Phe Phe Arg Phe Ala 175 180 185 Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val Leu Val Asp 190 195 200 Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg lie 205 210 215 Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe Gin Leu Leu Lys 220 225 230 Leu Trp Lys His Gin Asn Lys Asp Gin Asp lie Val Lys Lys lie 235 240 245 lie Gin Asp lie Asp Leu Cys Glu Asn Ser Val Gin Arg His lie 250 255 260 Gly His Ala Asn Leu Thr Phe Glu Gin Leu Arg Ser Leu Met Glu 265 270 275 Ser Leu Pro Gly Lys Lys Val Gly Ala Glu Asp lie Glu Lys Thr Staff Welfare Committee, Central Standards Bureau, Ministry of Economic Affairs Printed by the Committee 280 285 290 lie Lys Ala Cys Lys Pro Ser Asp Gin lie Leu Lys Leu Leu Ser 295 300 305 Leu Trp Arg Ile Lys Asn Gly Asp Gin Asp Thr Leu Lys Gly Leu 31〇315 320 Met His Ala Leu Lys His Ser Lys Thr Tyr Tyr His Phe Pro Lys Thr 325 330 335 This paper size applies to China National Standard (CNS) A4 (210 X 297 public love) 28 38076 538049 H3 Val Thr Gin Ser Leu printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs Lys Lys Thr lie Arg Phe Leu His Ser Phe 340 345 350 Thr Met Tyr Lys Leu Tyr Gin Lys Leu Phe Leu Glu Met lie Gly 355 360 365 Asn Gin Val Gin Ser Val Lys lie Ser Cys Leu 370 375 380. 25. —A cDNA encoding a protein that inhibits osteoclast formation, characterized by encoding the following amino acid sequence: This paper rule applies to the Chinese National Standard (CNS) A4 Regulation (210 X 297 mm) ^ 538049 H3 Met Asn Asn Leu Leu Cys Cys Ala Lea Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Fro Lys Tyr Leu His -5 -11 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35 ^ Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys TO 75 80 Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Leu Lys 85 90 95 His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala G-ly Thr 100 105 110 Pro Glu Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 115 120 125 Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs Chinese National Standard (CNS ) A4 size (210 X 297 mm) 30 38076 538049 H3 Printed by the Employee Welfare Committee of the Central Standards Bureau of the Ministry of Economy Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 130 135 140 Cys Ser Val Phe Gly Leu Leu Leu Thr Gin Lys Gly Asn Ala Thr 145 150 155 His Asp Asn lie Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Ser 160 165 170 Gly lie Asp Val Thr Leu Cys Glu Glu Ala Phe Phe Arg Phe Ala 175 180 185 Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val Leu Val Asp 190 195 200 Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg lie 205 210 215 Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe Gin Leu Leu Lys 220 225 230 Leu Trp Lys His Gin Asn Lys Asp Gin Asp lie Val Lys Lys lie 235 240 245 lie Gin Asp lie Asp Leu Cys Glu Asn Ser Val Gin Arg His lie 250 255 260 Gly His Ala Asn Leu Thr Phe Glu Gin Leu Arg Ser Leu Met Glu 265 270 275 Ser Leu Pro Gly Lys Lys Val Gly Ala Glu Asp lie Glu Lys Thr 280 285 290 lie Lys Ala Cys Lys Pro Ser Asp Gin lie Lea Lys Leu Lea Ser 295 300 305 Leu Trp Arg lie Lys Asn Gly Asp Gin Asp Thr Leu Lys Gly Leu 310 315 320 Met His Ala Leu Lys His Ser Lys Thr Tyr His Phe Pro Lys Thr 325 330 335 This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 31 38076 538049 H3 Val Thr Gin Ser Leu Lys Lys Thr lie Arg Phe Leu His Ser Phe 340 345 350 Thr Met Tyr Lys Leu Tyr Gin Lys Leu Phe Leu Glu Met lie Gly 355 360 365 Asn Gin Val Gin Ser Val Lys lie Ser Cys Leu 370 375 380 Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs 26. - encodings inhibit protein formation of osteoclasts of a cDNA shown in the following Salt yl sequence: ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TGTGACAAAT GTCCTCCTGG TACCTACCTA AAftCAACACT GTACAGCAAA GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GTTTGCAAAA GATGTCCAGA TGGGTTCTTC TCAAATGAGA CGTCATCTAA AGAAAACACA CAAATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG CACGACAACA TATGTTCCGG AAACAGTGAA TCAACTCAAA AATGTGGAAT CTGTGTGAGG AGGCATTCTT CAGGTTTGCT GTTCCTACAA AGTTTACGCC AGTGTCTTGG TAGACAATTT GCCTGGCACC AAAGTAAACG CAGAGAGTGT AAACGGCAAC ACAGCTCACA AGAACAGACT TTCCAGCTGC TGAAGTTATG AACAAAGACC AAGATATAGT CAAGAAGATC ATCCAAGATA TTGACCTCTG GTGCAGCGGC ACATTGGACA TGCTAACCTC ACCTTCGAGC AGCTTCGTAG AGCTTACCGG GAAAGAAAGT GGGAGCAGAA GACATTGAAA AAACAATAAA CCCAGTGACC AGATCCTGAA GCTGCTCAGT T TGTGGCGAA TAAAAAATGG ACCTTGAAGG GCCTAATGCA CGCACTAAAG CACTCAAAGA CGTACCACTT GTCACTCAGA GTCTAAAGAA GACCATCAGG TTCCTTCACA GCTTCACAAT TATCAGAAGT TATTTTTAGA AATGATAGGT AACCAGGTCC AATCAGTAAA TTATAA CDNA, characterized in GTGGACCACC 60 TCAGCTGTTG 120 GTGGAAGACC 180 TGACGftGTGT 240 CAATCGCACC 300 CTGCTTGAAA 360 GCGAAATACA 420 AGCACCCTGT 480 AAATGCAACA 540 AGATGTTACC 600 TAACTGGCTT 660 AGAGAGGATA 720 GAAACATCAA 780 TGAAAACAGC 840 CTTGATGGAA 900 GGCATGCAAA 960 CGACCAAGAC 1020 TCCCAAAACT 1080 GTACAAATTG 1140 AATAAGCTGC 1200 1206 0 2 7. — A species that inhibits human osteoclast formation and is composed of the following amino acid sequences. The first paper size applies the Chinese National Standard (CNS) A4 (210 X 297 mm). 32 Fine 76 538049 _ H3_ to 3 80 amino acids. The protein is obtained from the cDNA expression of item 26 of the patent application: Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -t0 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 -11 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35. Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80 Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Leu Lys 85 90 95 Gl Printed by the Staff Welfare Committee of the Central Bureau of Standards of the Ministry of Economy cy Mm) 33 38076 538049 H3 Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 130 135 140 Cys Ser Val Phe Gly Leu Leu Leu Thr Gin Lys Gly Asn Ala Thr 145 150 155 His Asp Asn lie Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Ser 160 165 170 Gly lie Asp Val Thr Leu Cys Glu Glu Ala Phe Phe Arg Phe Ala 175 180 185 Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val Leu Val Asp 190 195 200 Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg lie 205 210 215 Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe Gin Leu Leu Lys 220 225 230 Leu Trp Lys His Gin Asn Lys Asp Gin Asp li e Val Lys Lys lie 235 240 245 lie Gin Asp lie Asp Leu Cys Glu Asn Ser Val Gin Arg His lie 250 255 260 Gly His Ala Asn Leu Thr Phe Glu Gin Leu Arg Ser Leu Met Glu 265 270 275 Ser Leu Pro Gly Lys Lys Val Gly Ala Glu Asp lie Glu Lys Thr Printed by the Staff Welfare Committee of the Central Standards Bureau, Ministry of Economy 280 285 290 lie Lys Ala Cys Lys Pro Ser Asp Gin lie Leu Lys Leu Leu Ser 295 300 305 Leu Trp Arg lie Lys Asn Gly Asp Gin Asp Thr Leu Lys Gly Leu 310 315 320 Met His Ala Leu Lys His Ser Lys Thr Tyr His Phe Pro Lys Thr 325 330 335 This paper size applies to China National Standard (CNS) A4 (210 Xj297 mm) 34 38076 538049 Central Ministry of Economic Affairs Printed by the Staff Welfare Committee of the Standard Bureau_ H3_ Val Thr Gin Ser Leu Lys Lys Thr lie Arg Phe Leu His Ser Phe 340 345 350 Thr Met Tyr Lys Leu Tyr Gin Lys Leu Phe Leu Glu Met lie Gly 355 360 365 Asn Gin Val Gin Ser Val Lys lie Ser Cys Leu 370 375 380. 2 8. -A cDNA encoding a protein that inhibits osteoclast formation, characterized by encoding the following amino acid sequences: Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 -1 1 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35. Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80 Glu Cys Lys Glu Gly Arg Tyr Leu Glu He Glu Phe Cys Leu Lys 85 90 95 His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Grly Thr 100 105 110 Pro Glu Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 115 120 125 This paper size is in accordance with Chinese National Standard (CNS) A4 (210 X 297 mm) 35 38076 538049 H3 Printed by Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 130 135 140 Cys Ser Val Phe Gly Leu Leu Leu Thr Gin Lys Gly Asn Ala Thr 145 150 155 His Asp Asn lie Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Ser 160 165 170 Gly lie Asp Val Thr Leu Cys Glu Glu Glu Ala Phe Phe Arg Phe Ala 175 180 185 Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val Leu Val Asp 190 195 200 Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg lie 205 2 10 215 Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe Gin Leu Lea Lys 220 225 230 Leu Trp Lys His Gin Asn Lys Asp Gin Asp lie Val Lys Lys lie 235 240 245 lie Gin Asp lie Asp Leu Cys Glu Asn Ser Val Gin Arg His lie 250 255 260 Gly His Ala Asn Leu Thr Phe Glu Gin Leu Arg Ser Leu Met Glu 265 270 275 Ser Leu Pro Gly Lys Lys Vai Gly Ala Glu Asp lie Glu Lys Thr 280 285 290 lie Lys Ala Cys Lys Pro Ser Asp Gin lie Leu Lys Leu Leu Ser 295 300 305 Leu Trp Arg lie Lys Asn Gly Asp Gin Asp Thr Leu Lys Gly Leu 310 315 320 Met His Ala Leu Lys His Ser Lys Thr Tyr His Phe Pro Lys Thr 325 330 335 China National Standard (CNS) A4 (210 x 297 mm) 36 38076 538049 H3 Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economy Val Thr Gin Ser Leu Lys Lys Thr lie Arg Phe Leu His Ser Phe 340 345 350 Thr Met Tyr Lys Leu Tyr Gin Lys Leu Phe Leu Glu Met lie Gly 355 360 365 Asn Gin Val Gin Ser Val Lys lie Ser Cys Leu 370 375 380. 29. - encodings inhibition cDNA-protein formation of osteoclasts, wherein the cDNA shown below Salt yl sequence: ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACGTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAflGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTftCCTTG AGATAGAGTT CTGCTTGAAA 360 CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 GTTTGCAAAA GATGTCCAGA TGGGTTCTTC TCAAATGAGA CGTCATCTAA AGCACCCTGT 480 AGAAAACACA CAAATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG AAATGCAACA 540 CACGACAACA TATGTTCCGG AAACAGTGAA TCAACTCAAA AAAGTGGAAT AGATGTTACC 600 CTGTGTGAGG AGGCATTCTT CAGGTTTGCT GTTCCTACAA AGTTTACGCC TAACTGGCTT 660 AGTGTCTTGG TAGACAATTT GCCTGGCACC AAAGTAAACG CAGAGAGTGT AGAGAGGATA 720 AAACGGCAAC ACAGCTCACA AGAACAGACT TTCCAGCTGC TGAAGTTATG GA AACATCAA 780 AACAAAGACC AAGATATAGT CAAGAAGATC ATCCAAGATA TTGACCTCTG TGAAAACAGC 840 GTGCAGCGGC ACATTGGACA TGCTAACCTC ACCTTCGAGC AGCTTCGTAG CTTGATGGAA 900 AGCTTACCGG GAAAGAAAGT GGGAGCAGAA GACATTGAAA AAACAATAAA GGCATGCAAA 960 CCCAGTGACC AGATCCTGAA GCTGCTCAGT TTGTGGCGAA TAAAAAATGG CGACCAAGftC 1020 ACCTTGAAGG GCCTAATGCA CGCACTAAAG CACTCAAAGA CGTACCACTT TCCCAAAACT 1080 GTCACTCAGA GTCTAAAGAA GACCATCAGC TTCCTTCACA GCTTCACAAT GTACAAATTG 1140 TATCAGAAGT TATTTTTAGA AATGATAGGT AACCAGGTCC AATCAGTAAA AATAAGCTGC 1200 TTATAA 1206. 3 0 · —A protein that inhibits human osteoclast formation and is composed of the following amino acid sequences Nos. 1 to 3 80 amino acids, which is covered by the scope of patent application No. 29 This paper applies Chinese national standard (CNS) A4 specifications (210 X 297 mm) 37 38076 538049 H3 cDNA expression obtained: Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 -1 1 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35 Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80 Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Leu Lys 85 90 95 His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala & ly Thr 100 105 110 Pro Glu Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Fhe Staff, Central Bureau of Standards, Ministry of Economic Affairs The paper size printed by the Profits Committee applies the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 538049 H3 Printed by the Employee Welfare Committee of the Central Standards Bureau of the Ministry of Economy Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 130 135 140 Cys Ser Val Phe Gly Leu Leu Leu Thr Gin Lys Gly Asn Ala Thr 145 150 155 His Asp Asn lie Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Ser 160 165 170 Gly lie Asp Val Thr Leu Cys Glu Glu Ala Phe Phe Arg Phe Ala 175 180 185 Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val Leu Val Asp 190 195 200 Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg lie 205 210 215 Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe Gin Leu Leu Lys 220 225 230 Leu Trp Lys His Gin Asn Lys Asp Gin Asp lie Val Lys Lys lie 235 240 245 lie Gin Asp lie Asp Leu Cys Glu Asn Ser Val Gin Arg His lie 250 255 260 Gly His Ala Asn Leu Thr Phe Glu Gin Leu Arg Ser Leu Met Glu 265 270 275 Ser Leu Pro Gly Lys Lys Val Gly Ala Glu Asp lie Glu Lys Thr 280 285 290 lie Lys Ala Cys Lys Pro Ser Asp Gin lie Leu Lys Leu Leu Ser 295 300 305 Leu Trp Arg lie Lys Asn Gly Asp Gin Asp Thr Leu Lys Gly Leu 310 315 320 Met His Ala Leu Lys His Ser Lys Thr Tyr His Phe Pro Lys Thr 325 330 335 (CNS) A4 size (210 x 297 mm) 39 38076 538049 Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs _ H3__ Val Thr Gin Ser Leu Lys Lys Thr lie Arg Phe Leu His Ser Phe 340 345 350 Thr Met Tyr Lys Leu Tyr Gin Lys Leu Phe Leu Glu Met lie Gly 355 360 365 Asn Gin Val Gin Ser Val Lys lie Ser Cys Leu 370 375 380. 3 1. -A cDNA encoding a protein that inhibits osteoclast formation, characterized by encoding the following amino acid sequences: Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 -11 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35. Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80 Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Leu Lys 85 90 95 His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala & ly Thr 100 105 110 Pro Glu Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 115 120 125 This paper size applies to Chinese National Standard (CNS) A4 (210 X 297 mm) 40 38076 538049 H3 Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 130 135 140 Cys Ser Val Phe Gly Leu Leu Leu Thr Gin Lys Gly Asn Ala Thr 145 150 155 His Asp Asn lie Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Ser 160 165 170 Gly lie Asp Val Thr Leu Cys Glu Glu Ala Phe Phe Arg Phe Ala 175 180 185 Val. Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val Leu Val Asp 190 195 200 Asn Lea Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg lie 205 210 215 Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe Gin Leu Leu Lys 220 225 230 Leu Trp Lys His Gin Asn Lys Asp Gin Asp lie Val Lys Lys lie 235 240 245 lie Gin A $ p lie Asp Leu Cys Glu Asn Ser Val Gin Arg His lie 250 255 260 Gly His Ala Asn Leu Thr Phe Glu Gin Leu Arg Ser Leu Met Glu 265 270 275 Ser Leu Pro Gly Lys Lys Val Gly Ala Glu Asp lie Glu Lys Thr 280 285 290 lie Lys Ala Cys Lys Pro Ser Asp Gin lie Leu Lys Leu Leu Ser 295 300 305 Leu Trp Arg He Lys Asn Gly Asp Gin Asp Thr Leu Lys Gly Leu 31〇315 320 Met His Ala Leu Lys His Ser Lys Thr Tyr His Phe Pro Lys Thr 325 330 335 This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) ) 41 38076 538049 H3 Printed clothing Val Thr Gin Ser Leu Lys Lys Thr lie Arg Phe Leu His Ser Phe 340 345 350 Thr Met Tyr Lys Leu Tyr Gin Lys Leu Phe Leu Glu Met Het e Gly 355 360 365 Asn Gin Val Gin Ser Val Lys lie Ser Cys Leu 370 375 380. 3 2. - encodings inhibition cDNA-protein formation of osteoclasts, wherein the cDNA shown below Salt yl sequence: ATGMCAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACftACACT GTACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 CTSTACTGCS GCCCCGTGTG CftAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 GTTTGCAAAA GATGTCCAGA TGGGTTCTTC TCAAATGAGA CGTCATCTAA AGCACCCTGT 480 AGAAAACACA CAAATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG AAATGCAACA 540 CACGACAACA TATGTTCCGG AAACAGTGAA TCAACTCAAA AAAGTGGAAT AGATGTTACC 600 CTGTGTGAGG AGGCATTCTT CAGGTTTGCT GTTCCTACAA AGTTTACGCC TAACTGGCTT 660 AGTGTCTTGG TAGACAATTT GCCTGGCACC AAAGTAAACG CAGAGAGTGT AGAGAGGATA 720 AAACGGCAAC ACAGCTCACA AGAACAGACT TTCCAGCTGC TGAAGTTATG GAA ACATCAA 780 AACAAAGACC AAGATATAGT CAAGAAGATC ATCCAAGATft TTGACCTCTG TGAAAACAGC 840 GTGCAGCGGC ACATTGGACA TGCTAACCTC ACCTTCGAGC AGCTTCGTAG CTTGATGGAA 900 AGCTTACCGG GAAAGAAAGT GGGAGCAGAA GACATTGAAA AAACAATAAA GGCATGCAAA 960 CCCAGTGACC AGATCCTGAA GCTGCTCAGT TTGTGGCGAA TAAAAAATGG CGACCAAGAC 1020 ACCTTGAAGG GCCTAATGCA CGCACTAAAG CACTCAAAGA CGTACCACTT TCCCAAAACT 1080 GTCACTCAGA GTCTAAAGAA GACCATCAGG TTCCTTCACA GCTTCftCAAT GTACAAATTG 1140 TATCAGAAGT TATTTTTAGA AATGATSGGT AACC4GGTCC AATCAGTAAA AATAAGCTGC 1200 TTATAA 1206 '33. —A protein that inhibits the formation of human osteoclasts and is composed of the following amino acid sequences Nos. 1 to 3 80, which is the 32th in the scope of the patent application. This paper is applicable to the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 42 38076 538049 H3 • cDNA performance of the item: Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 -11 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35. Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80 Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Leu Lys 85 90 95 His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala G-ly Thr 100 105 110 Pro Glu Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe Printed by the Staff Welfare Committee of the Central Bureau of Standards, Ministry of Economic Affairs Paper size applies to Chinese National Standard (CNS) A4 (210 X 297 mm) 43 38076 538049 H3 Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 130 135 140 Cys Ser Val Phe Gly Leu Leu Leu Thr Gin Lys Gly Asn Ala Thr 145 150 155 His Asp Asn lie Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Ser 160 165 170 Gly lie Asp Val Thr Leu Cys Glu Glu Ala Phe Phe Arg Phe Ala 175 180 185 Val. Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val Leu Val Asp 190 195 200 Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg lie 205 210 215 Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe Gin Leu Leu Lys 220 225 230 Leu Trp Lys His Gin Asn Lys Asp Gin Asp lie Val Lys Lys lie 235 240 245 He Gin Asp lie Asp Leu Cys Glu Asn Ser Val Gin Arg His lie 250 255 260 Gly His Ala ftsn Leu Thr Phe Glu Gin Leu Arg Ser Leu Met Glu 265 270 275 Ser Leu Pro Gly Lys Lys Val Gly Ala Glu Asp lie Glu Lys Thr Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs 280 285 290 lie Lys Ala Cys Lys Pro Ser Asp Gin lie Leu Lys Leu Leu Seru 295 300 305 Leu Trp Arg lie Lys Asn Gly Asp Gin Asp Thr Leu Lys Gly Leu 310 315 320 Met His Ala Leu Lys His Ser Lys Thr Tyr Tyr His Phe Pro Lys Thr 325 330 335 This paper is in accordance with the Chinese National Standard (CNS) A4 Specifications (210 X 297 mm) 44 38076 538049 Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs_H3_. Val Thr Gin Ser Leu Lys Lys Thr lie Arg Phe Leu His Ser Phe 340 345 350 Thr Met Tyr Lys Leu Tyr Gin Lys Leu Phe Leu Glu Met lie Gly 355 360 365 Asn Gin Val Gin Ser Val Lys lie Ser Cys Leu 370 375 380 . 34. -A cDNA encoding a protein that inhibits osteoclast formation, characterized by encoding the following amino acid sequences: Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 -11 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gla His Cys Thr Ala Lys Trp Lys Thr 25 30 35 t Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Giu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80 Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Lea Lys 85 90 95 His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala & ly Thr 100 105 110 Pro Glu Arg Asm Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 115 120 125 This paper size applies to Chinese National Standard (CNS) A4 (210 X 297 mm) 45 38076 538049 H3 Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 130 135 140 Cys Ser Val Ph e Gly Leu Leu Leu Thr Gin Lys Gly Asn Ala Thr 145 150 155 His Asp Asn lie Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Ser 160 165 170 Gly lie Asp Val Thr Leu Cys Glu Glu Ala Phe Phe Arg Phe Ala 175 180 185 Val. Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val Leu Val Asp 190 195 200 Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg lie 205 210 215 Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe Gin Leu Leu Lys 220 225 230 Leu Trp Lys His Gin Asn Lys Asp Gin Asp lie Val Lys Lys lie 235 240 245 He Gin Asp lie Asp Leu Cys Glu Asn Ser Val Gin Arg His lie 250 255 260 Gly His Ala Asn Leu Thr Phe Glu Gin Leu Arg Ser Leu Met Glu 265 270 275 Ser Leu Pro Gly Lys Lys Val Gly Ala Glu Asp lie Glu Lys Thr Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs 280 285 290 He Lys Ala Cys Lys Pro Ser Asp Gin lie Leu Lys Leu Leu Seru 295 300 305 Leu Trp Arg He Lys Asn Gly Asp Gin Asp Thr Leu Lys Gly Leu 310 315 320 His Ala Leu Lys His Ser Lys Thr Tyr His Phe Pro Lys Thr 335 330 325 This paper size applies to China National Standard (CNS) A4 specifications (210 X 297 mm) 46 38076 538049 H3. Val Thr Gin Ser Leu Lys Lys Thr lie Arg Phe Leu His Ser Phe 340 345 350 Thr Met Tyr Lys Leu Tyr Gin Lys Leu Phe Leu Glu Met lie Gly 355 360 365 Asn Gin Val Gin Ser Val Lys lie Ser Cys Leu 370 375 380 〇35. -A cDNA encoding a protein that inhibits osteoclast formation, which is characterized by the following cDNA sequence: ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAGCACACCCGTCCACCTCCACCT TGACGAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA employee benefits Committee of economic Affairs Bureau of standards 360 printed CATAGGAGCT GCCCTCCTGG ftTTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 GTTTGCAAAA GATGTCCAGA TGGGTTCTTC TCAAATGAGA CGTCATCTAA AGCACCCTGT 480 AGAAAACACA CAAATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG AAATGCAACA 540 CACGACAACA TATGTTCCGG AAACAGTGAA TCAACTCAAA AAAGTGGAAT AGATGTTACC 600 CTGTGTGAGG AGGCATTCTT CAGGTTTGCT GTTCCTACAA AGTTTACGCC TAACTGGCTT 660 AGTGTCTTGG TAGACAATTT GCCTGGCACC AAAGTAAACG CAGAGAGTGT AGAGAGGAT A 720 AAACGGCAAC ACAGCTCACA AGAACAGACT TTCCAGCTGC TGAAGTTATG GAAACATCAA 780 AACAAAGACC AAGATATAGT CAAGAAGATC ATCCAAGATA TTGACCTCTG TGAAAACAGC 840 GTGCAGCGGC ACATTGGACA TGCTAACCTC ACCTTCGAGC AGCTTCGTAG CTTGATGGAA 900 AGCTTACCGG GAAAGAAAGT GGGAGCAGAA GACATTGAAA AAACAATAAA GGCATGCAAA 960 CCCAGTGACC AGATCCTGAA GCTGCTCAGT TTGTGGCGAA TAAAAAATGG CGACCAAGAC 1020 ACCTTGAAGG GCCTAATGCA CGCACTAAAG CACTCAAAGA CGTACCACTT TCCCAAAACT 1080 GTCACTCAGA GTCTAAAGAA GACCATCflGG TTCCTTCACA GCTTCACAAT GTACAAATTG 1140 TATCAGAAGT TATTTTTAGA AATGATAGGT AACCAGGTCC AATCAGTAAA AATAAGCTGC 1200 TTATAA 1206. 36. —A protein that inhibits the formation of human osteoclasts and consists of the following amino acid sequences Nos. 1 to 3 80, which is the 35th in the scope of the patent application. This paper is applicable to the Chinese National Standard (CNS) A4 (210 X 297 mm) 47 38076 538049 H3 cDNA performance winner: Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 -11 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35. Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Fro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80 Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Lea Lys 85 90 95 His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala G-ly Thr 100 105 110 Pro Glu Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs This paper is printed in accordance with the Chinese National Standard (CNS) A4 (210 X 297 mm) 48 38076 538049 H3 Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 130 135 140 Cys Ser Val Phe Gly Leu Leu Leu Thr Gin Lys Gly Asn Ala Thr 145 150 155 His Asp Asn lie Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Ser 160 165 170 Gly lie Asp Val Thr Leu Cys Glu Glu Ala Phe Phe Arg Phe Ala 175 180 185 Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val Leu Val Asp 190 195 200 Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg lie 205 210 215 Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe Gin Leu Leu Lys 220 225 230 Leu Trp Lys His Gin Asn Lys Asp Gin Asp lie Val Lys Lys lie 235 240 245 lie Gin Asp lie Asp Leu Cys Glu Asn Ser Val Gin Arg His lie 250 255 260 Gly His Ala Asn Leu Thr Phe Glu Gin Leu Arg Ser Leu Met Glu 265 270 275 Ser Leu Pro Gly Lys Lys Val Gly Ala Glu Asp lie Glu Lys Thr 280 285 290 lie Lys Ala Cys Lys Pro Ser Asp Gin lie Leu Lys Leu Leu Ser 295 300 305 Lea Trp Arg lie Lys Asn Gly Asp Gin Asp Thr Leu Lys Gly Leu 310 315 320 Met His Ala Leu Lys His Ser Lys Thr Tyr His Phe Pro Lys Thr 325 330 335 This paper size applies to Chinese National Standard (CNS) A4 (210 X 297 mm) 49 38076 538049 H3 Printed by Val Thr Gin Ser Leu Lys Lys Thr lie Arg Phe Leu His Ser Phe 340 345 350 Thr Met Tyr Lys Leu Tyr Gin Lys Leu Phe Leu Glu Met lie Gly 355 360 365 Asn Gin Val Gin Ser Val Lys lie Ser Cys Leu 370 375 380. 37. -A cDNA encoding a protein that inhibits osteoclast formation, characterized by encoding the following amino acid sequences: Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Fhe Pro Pro Lys Tyr Leu His -5 -1 1 5 Tyr Asp Gin Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35. Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80 Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Lea Lys 85 90 95 His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala & ly Thr 100 105 110 Pro Glu Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Fhe 115 120 125 This paper size applies to Chinese National Standard (CNS) A4 (210 X 297 mm) 50 38076 538049 H3 Printed by Ser Asn GIu Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 130 135 140 Cys Ser Val Phe Gly Leu Leu Leu Thr Gin Lys Gly Asn Ala Thr 145 150 155 His Asp Asn lie Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Ser 160 165 170 Gly lie Asp Val Thr Leu Cys Glu Glu Ala Phe Phe Arg Phe Ala 175 180 185 Val, Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val Leu Val Asp 190 195 200 Asn Lea Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg lie205 210 215 Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe Gin Leu Lea Lys 220 225 230 Leu Trp Lys His Gin Asn Lys Asp Gin Asp lie Val Lys Lys lie 235 240 245 lie Gin Asp lie Asp Leu Cys Glu Asn Ser Val Gin Arg His lie 250 255 260 Gly His Ala Asn Leu Thr Phe Glu Gin Leu Arg Ser Leu Met Glu 265 270 275 Ser Leu Pro Gly Lys Lys Val Gly Ala Glu Asp lie Glu Lys Thr 280 285 290 lie Lys Ala Cys Lys Pro Ser Asp Gin lie Leu Lys Leu Leu Ser 295 300 305 Leu Trp Arg lie Lys Asn Gly Asp Gin Asp Thr Leu Lys Gly Leu 310 315 320 Met His Ala Leu Lys His Ser Lys Thr Tyr His Phe Pro Lys Thr 325 330 335 Paper Size Applicable to China National Standard (CNS) A4 (210 X 297 mm) 51 38076 538049 H3 Val Thr Gin Ser Leu Lys Thr lie Arg Phe Leu His Ser Phe 340 345 350 Thr Met Tyr Lys Leu Tyr Gin Lys Leu Phe Leu Glu Met lie Gly 355 360 365 Asn Gin Val Gin Ser Val Lys lie Ser Cys Leu 370 375 380 〇38. A cDNA encoding a protein that inhibits osteoclast formation, which is characterized by the following cDNA sequences: GTGGACCACC 60 CGAGTGTCTA 120 TCGCACCCAC 180 CTTGAAACAT 240 AAATACAGTT 300 ACCCTGTAGA 360 TGCAACACAC 420 TGTTACCCTGG 480 CTGGCTTAGT 540 GAGGATAAAA 600 ACATCGAACAC TAC 660 AAA AACCGCGTGT AGGAGCTGCC TGCAAAAGAT AAACACACAA GACAACATAT TGTGAGGAGG GTCTTGGTAG CGGCAACACA AAAGACCAAG TGCTGTGCTG GCCCTGACCA CCGTGTGCAA GCGAATGCAA CTCCTGGATT GTCCAGATGG ATTGCAGTGT GTTCCGGAAA CATTCTTCAG ACAATTTGCC GCTCACAAGA ATATAGTCAA CGCGCTCGTG CTACTACACA GGAGCTGCAG GGAAGGGCGC TGGAGTGGTG GTTCTTCTCA CTTTGGTCTC CAGTGAATCA GTTTGCTGTT TGGC4CCAAA ACAGACTTTC GAAGATCATC TTTCTGGACA GACAGCTGGC TACGTCAAGC TACCTTGAGA CAAGCTGGAA AATGAGACGT CTGCTAACTC ftCTCAAAAAT CCTACAAAGT GTAAACGCAG CAGCTGCTGA CAAGATATTG TCTCCATTM ACACCAGTGA AGGAGTGCAA TAGAGTTCTG CCCCAGAGCG CATCTAAAGC AGAAAGGAAA GTGGAATAGfl TTACGCCTAA AGAGTGTAGA AGTTATGGAA ACCTCTGTGA Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs CAGCGGCACA TTGGACATGC TAACCTCACC TTCGAGCAGC TTCGTAGCTT GATGGAAAGC 780 TTACCGGGAA AGAAAGTGGG AGCAGAAGAC ATTGAAAAAA CAATAAAGGC ATGCAAACCC 840 AGTGACCAGA TCCTGAAGCT GCTCAGTTTG TGGCGAATAA AAAATGGCGA CCAAGACACC 900 TTCAAGGGCC TAATGCACGC ACTAAAGCAC TCAAAGACGT ACCACTTTCC CAAAACTGTC 960 ACTCAGAGTC TAAAGAAGAC CATCAGGTTC CTTCACAGCT TCACAATGTA CAAATTGTAT 1020 CAGAAGTTAT TTTTAGAAAT GATAGGTAAC CAGGTCCAAT CAGTAAAAAT AAGCTGCTTA 1080 TAA 1083 3 9. —A protein that inhibits human osteoclast formation and is composed of the following amino acid sequences Nos. 1 to 339, which is the 38th in the scope of the patent application. This paper applies the Chinese National Standard (CNS) A4 specification (210 x 297 (Mm) 52 38076 538049 ___H3_ winner of c DNA performance Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asplle Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Pro Cys Pro Asp His Tyr Tyr Thr -5 -1 1 5 Asp Ser Trp His Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro VaL 10 15 20 Cys Lys Glu Leu Gin Tyr Val Lys Gla Glu Cys Asn Arg Thr His 25 _ 30 35 Asn Arg Val Cys Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu 40 45 50 Phe Cys Lea Lys His Arg Ser Cys Pro Pro Gly Phe Gly Val Val 55 60 65 Gin Ala Gly Thr Pro Glu Arg Asn Thr Val Cys Lys Arg Cys Pro 70 75 80 Asp Gly Phe Phe Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys Arg 85 90 95 Lys His Thr Asn Cys Ser Val Phe Gly Leu Leu Leu Thr Gin Lys 100 105 110 Printed by the Staff Welfare Committee of the Central Bureau of Standards of the Ministry of Economics This paper is applicable to China Standard (CN S) A4 size (210 X 297 mm) 53 38076 538049 H3 Gly Asn Ala Thr His Asp Asn lie Cys Ser Gly Asn Ser Glu Ser 115 120 125 Thr Gin Lys Cys Gly lie Asp Val Thr Leu Cys Glu Glu Ala Phe 130 135 140 Phe Arg Phe Ala Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser 145 150 155 Val Leu Val Asp Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser 160 165 170 Vai Glu Arg lie Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe 175 '180 185 Gin Leu Leu Lys Leu Trp Lys His Gin Asn Lys Asp Gin Asp lie 190 195 200 Val Lys Lys lie lie Gin Asp lie Asp Leu Cys Glu Asn Ser Val 205 210 215 Gin Arg His lie Gly His Ala Asn Leu Thr Phe Glu Gin Leu Arg * 220 225 230 Ser Leu Met Glu Ser Leu Pro Gly Lys Lys Val Gly Ala Glu Asp 235 240 245 lie Glu Lys Thr lie Lys Ala Cys Lys Pro Ser Asp Gin lie Leu 250 255 260 Lys Leu Leu Ser Leu Trp Arg lie Lys Asn Gly Asp Gin Asp Thr 265 270 275 Printed by Lea Lys Gly Leu Met His Ala Leu Lys His Ser Lys Thr Tyr His 280 285 290 Phe Pro Lys Thr Val Thr Gin Ser Leu Lys Lys Thr lie Arg Phe 295 300 305 Lea His Ser Phe Thr Met Tyr Lys Leu Tyr Gin Lys Leu Phe Leu 310 315 320 Glu Met lie Gly Asn Gin Val Gin Ser Val Lys lie Ser Cys Leu 325 330 335. 40. —A cDNA encoding a protein that inhibits osteoclast formation. The characteristics of this paper are applicable to the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 54 38076 538049 _H3_ are those encoding the following amino acid sequences: Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp-Ile Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Pro Cys Pro Asp His Tyr Tyr Thr -5 -11 5 Asp Ser Trp His Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro VaL 10 15 20 Cys Lys Glu Leu Gin Tyr Val Lys Glo Glu Cys Asn Arg Thr His 25 _ 30 35 Asn Arg Val Cys Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu 40 45 50 Phe Cys Leu Lys His Arg Ser Cys Pro Pro Gly Phe Gly Val Val 55 60 65 Gin Ala Gly Thr Pro Gla Arg Asn Thr Val Cys Lys Arg Cys Pro 70 75 80 Asp Gly Phe Phe Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys Arg 85 90 95 Lys His Thr Asn Cys Ser Val Phe Gly Leu Leu Leu Thr Gin Lys 100 105 110 Printed by the Staff Welfare Committee of the Central Bureau of Standards of the Ministry of Economic Affairs This paper is sized for the Chinese National Standard (CNS) A4 (210 X 297 mm) 55 38076 538049 H3 Gly Asn Ala Thr His Asp Asn lie Cys Ser Gly Asn Ser Glu Ser 115 120 125 Thr Gin Lys Cys Gly lie Asp Val Thr Leu Cys Glu Glu Ala Phe 130 135 140 Phe Arg Phe Ala Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser 145 150 155 Val Leu Val Asp Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser 160 165 170 Val Glu Arg lie Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe 175 '180 185 Gin Leu Lea Lys Leu Trp Lys His Gin Asn Lys Asp Gin Asp lie 190 195 200 Val Lys Lys lie lie Gin Asp lie Asp Leu Cys Glu Asn Ser Val 205 210 215 Gin Arg His lie Gly His Ala Asn Leu Thr Phe Glu Gin Leu Arg * 220 225 230 Ser Leu Met Glu Ser Leu Pro Gly Lys Lys Val Gly Ala Glu Asp 235 240 245 lie Glu Lys Thr lie Lys Ala Cys Lys Pro Ser Asp Gin lie Leu 250 255 260 Lys Leu Leu Ser Leu Trp Arg lie Lys Asn Gly Asp Gin Asp Thr 265 270 275 Ministry of Economy Printed by the Staff Welfare Committee of the Central Bureau of Standards Leu Lys Gly Leu Met His Ala Leu Lys His Ser Lys Thr Tyr His 280 285 290 Phe Pro Lys Thr Val Thr Gin Ser Leu Lys Lys Thr lie Arg Phe 295 300 305 Leu His Ser Phe Thr Met Tyr Lys Leu Tyr Gin Lys Leu Phe Leu 310 315 320 Glu Met lie Gly Asn Gin Val Gin Ser Val Lys He Ser Cys Leu 325 330 335. 41. A cDNA encoding a protein that inhibits the formation of osteoclasts. The characteristics of this paper are in accordance with Chinese National Standard (CNS) A4 (210 X 297 mm) 56 38076 538049 H3 The following are printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs cDNA sequence shown: ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGftCC 180 GTGTGCGCCG AATGCAAGGA AGGGCGCTAC CTTGAGATAG AGTTCTGCTT GAAACATAGG 240 AGCTGCCCTC CTGGATTTGG AGTGGTGCAA GCTGGAACCC CAGAGCGAAA TACAGTTTGC 300 AAAAGATGTC CAGATGGGTT CTTCTCAAAT GAGACGTCAT CTAAAGCACC CTGTAGAAAA 360 CACACAAATT GCAGTGTCTT TGGTCTCCTG CTAACTCAGA AAGGAAATGC AACACACGAC 420 AACATATGTT CCGGAAACAG TGAATCAACT CAAAAATGTG GAATAGATGT TACCCTGTGT 480 GAGGAGGCAT TCTTCAGGTT TGCTGTTCCT ACAAAGTTGTCC CGCCTAGCGCCAGCGCGCGCCAGCGCGCCAGCGCAGCAGCAGGCGCAGCA TATGGftAACA TCAAAACAAA 660 GACCAAGATA TAGTCAAGAA GATCATCCAA GATATTGACC TCTGTGAAAA CAGCGTGCAG 720 CGGCACATTG GACATGCTAA CCTCACCTTC GAGCAGCTTC GTAGCTTGAT GGAAAGCTTA 780 CCGGGAAAGA AAGTGGGAGC AGAAGACATT GAAAAAACAA TAAAGGCATG CAAACCCAGT 840 GACCAGATCC TGAAGCTGCT CAGTTTGTGG CGAATAAAAA ATGGCGACCA AGACACCTTG 900 AAGGGCCTAA TGCACGCAGT AAAGCACTCA AAGACGTACC ACTTTCCCAA AACTGTCACT 960 CAGAGTCTAA AGAAGACCAT CAGGTTCCTT CACAGCTTCA CAATGTACAA ATTGTATCAG 1020 AAGTTATTTT TAGAAATGAT AGGTMCCAG GTCCAATCAG TAMAATAAG CTGCTTATAA 1080. 42. —A kind of protein that inhibits human osteoclast formation and is composed of the following amino acid sequences Nos. 1 to 338, which are obtained from the cDNA expression of the 41st patent application scope: The paper size applies to Chinese national standards ( CNS) A4 size (210 X 297 mm) 57 38076 538049 H3 Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp He Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 -1 1 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Lea Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35 Val · Cys Ala Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe 40 45 50 Cys Leu Lys His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin 55 60 65 Ala Gly Thr Pro Glu Arg Asn Thr Val Cys Lys Arg Cys Pro Asp 70 75 80 Gly Phe Phe Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys Arg Lys 85 90 95 His Thr Asn Cys Ser Val Phe Gly Leu Leu Leu Le Thr Gin Lys Gly 100 105 110 Standard (CNS) A4 Specifications (210 X 297 mm) 58 38076 538049 H3 Asn Ala Thr His Asp Asn Lie Cys Ser Gly Asn Ser Glu Ser Thr 115 120 125 Gin Lys Cys Gly lie Asp Val Thr Leu Cys Glu Glu Ala Phe Phe 130 135 140 Arg Phe Ala Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val 145 150 155 Leu Val Asp Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val 160 165 170 Glu Arg lie Lys Arg Gla His Ser Ser Gin Glu Gin Thr Phe Gin 175 180 185 Leu Leu Lys Leu Trp Lys His Gin Asn Lys Asp Gin Asp lie Val 190 135 200 Lys Lys lie lie Gin Asp lie Asp Leu Cys Glu Asn Ser Val Gin 205 210 215 Arg His lie Gly His Ala Asn Leu Thr Phe Glu Gin Leu Arg Ser 220 225 230 Lea Met Glu Ser Leu Pro Gly Lys Lys Val Gly Ala Glu Asp lie 235 240 245 Glu Lys Thr lie Lys Ala Cys Lys Pro Ser Asp Gin lie Leu Lys 250 255 260 Leu Leu Ser Leu Trp Arg lie Lys Asn Gly Asp Gin Asp Thr Leu 265 270 275 Lys Gly Leu Met His Ala Leu Lys His Ser Lys Thr Tyr His Phe 280 285 290 Pro Lys Thr Val Thr Gin Ser Leu Lys Lys Thr lie Arg Phe Leu 295 300 305 His Ser Phe Thr Met Tyr Lys Leu Tyr Gin Lys Leu Phe Leu Glu 310 315 320 Met lie Gly Asn Gin Val Gin Ser Val Lys lie Ser Cys Leu 325 330 335 43.-Code Characteristics of cDNA that inhibits the formation of osteoclasts. The paper size applies the Chinese National Standard (CNS) A4 (210 X 297 mm) 59 38076 Boxing 538049 H3 is the one encoding the following amino acid sequence: Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5] 1 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Prp 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25. 30 35 Val Cys Ala Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe 40 45 50 Cys Leu Lys His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin 55 60 65 Ala Gly Thr Pro Glu Arg Asn Thr Val Cys Lys Arg Cys Pro Asp 70 75 80 Gly Phe Phe Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys Arg Lys 85 90 95 His Thr Asn Cys Ser Val Phe Gly Leu Leu Leu Tu Gin Lys Gly 100 105 110 Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs Paper size for printing is applicable to Chinese National Standard (CNS) A4 (210 X 297 mm) 60 38076 538049 H3 Asn Ala Thr His Asp Asn lie Cys Ser Gly Asn Ser Glu Ser Thr 115 120 125 Gin Lys Cys Gly lie Asp Val Thr Leu Cys Glu Glu Ala Phe Phe 130 135 140 Arg Phe Ala Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val 145 150 155 Leu Val Asp Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val 160 165 170 Glu Arg lie Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe Gin 175 '180 185 Leu Leu Lys Leu Trp Lys His Gin Asn Lys Asp Gin Asp lie Val 190 195 200 Lys L ys lie lie Gin Asp lie Asp Leu Cys Glu Asn Ser Val Gin 205 210 215 Arg His lie Gly His Ala Asn Lea Thr Phe Glu Gin Leu Arg Ser 220 225 230 Lea Met Glu Ser Lea Pro Gly Lys Lys Val Gly Ala Glu Asp lie 235 240 245 Glu Lys Thr lie Lys Ala Cys Lys Pro Ser Asp Gin lie Leu Lys 250 255 260 Leu Lea Ser Leu Trp Arg lie Lys Asn Gly Asp Gin Asp Thr Leu 265 270 275 Lys Gly Leu Met His Ala Leu Lys His Ser Lys Thr Tyr His Phe 280 285 290 Pro Lys Thr Val Thr Gin Ser Leu Lys Lys Thr lie Arg Phe Leu 295 300 305 His Ser Phe Thr Met Tyr Lys Leu Tyr Gin Lys Leu Phe Leu Glu 310 315 320 Met lie Gly Asn Gin Val Gin Ser Val Lys lie Ser Cys Leu 325 330 335. 44. A CDNA encoding a protein that inhibits the formation of osteoclasts. The paper size is applicable to Chinese National Standard (CNS) A4 (210 X 297 mm) 61 38076 538049 Printed by H3_ •• The following Salt base sequence cDNA: ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCAGATG TCCAGATGGG TTCTTCTCAA ATGAGACGTC ATCTAAAGCA 360 CCCTGTAGAA AACACACAAA TTGCAGTGTC TTTGGTCTCC TGCTAACTCA GAAAGGAAAT 420 GCAACACACG ACAACATATG TTCCGGAAAC AGTGAATCAA CTCAAAAATG TGGAATAGAT 480 GTTACCCTGT GTGAGGAGGC ATTCTTCAGG TTTGCTGTTC CTACAAAGAGCACACACATGAC GCTGCTGAft GTTATGGAAA 660 CATCAAAACA AAGACCAAGA TATAGTCAAG AAGATCATCC AAGATATTGA CCTCTGTGAA 720 AACAGCGTGC AGCGGCACAT TGGACATGCT AACCTCACCT TCGAGCAGCT TCGTAGCTTG 780 ATGGAAAGCT TACCGGGAAA GAAAGTGGGA GCAGAAGACA TTGAAAAAAC AATAAAGGCA 840 TGCAAACCCA GTGACCAGAT CCTGAAGCTG CTCAGTTTGT GGCGAATAAA AAATGGCGAC 900 CAAGACACCT TGAAGGGCCT AATGCACGCA CTAAAGCACT CAAAGACGTA CCACTTTCCC 960 AAAACTGTCA CTCAGAGTCT AAAGAAGACC ATCAGGTTCC TTCACAGCTT CACAATGTAC 1020 AAATTGTATC AGAAGTTATT TTTAGAAATG ATAGGTAACC AGGTCCAATC AGTAAAAATA 1080 AGCTGCTTAT AA 1092. 45. —A protein that inhibits human osteoclast formation and is composed of the following amino acid sequences Nos. 1 to 342, which are derived from the cDNA expression of item 44 of the scope of patent application: This paper size applies Chinese national standards ( CNS) A4 size (210 X 297 mm) 62 38076 538049 H3 Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 -11 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35 Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80 Arg Cys Fro Asp Gly Phe Phe Ser Asn Gla Thr Ser Ser Lys Ala 85 90 95 Pro Cys Arg Lys His Thr Asn Cys Ser Val Phe Gly Leu Leu Leu 100 105 110 CNS) A4 Grid (210 X 297 mm) 63 38076 538049 H3 Thr Gin Lys Gly Asn Ala Thr His Asp Asn lie Cys Ser Gly Asn 115 120 125 Ser GIu Ser Thr Gin Lys Cys Gly lie Asp Val Thr Lea Cys Glu 130 135 140 Glu Ala Phe Phe Arg Phe Ala Val Pro Thr Lys Phe Thr Pro Asn 145 150 155 Trp Leu Ser Val Leu Val Asp Asn Leu Pro Gly Thr Lys Val Asn 160 165 170 Ala. Glu Ser Val Glu Arg lie Lys Arg Gin His Ser Ser Gin Glu 175 180 185 Gin Thr Phe Gin Leu Leu Lys Leu Trp Lys His Gin Asn Lys Asp 190 195 200 Gin Asp lie Val Lys Lys lie lie Gin Asp lie Asp Leu Cys Glu 205 210 215 Asn Ser Val Gin Arg His lie Gly His Ala Asn Leu Thr Fhe Glu 220 225 230 Gin Leu Arg Ser Leu Met Glu Ser Leu Pro Gly Lys Lys Val Gly 235 240 245 Ala Glu Asp lie Glu Lys Thr lie Lys Ala Cys Lys Pro Ser Asp 250 255 260 Gin lie Leu Lys Leu Leu Ser Leu Trp Arg lie Lys Asn Gly Asp Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs 265 270 275 Gin Asp Thr Leu Lys Gly Leu Met His Ala Leu Lys His Ser Lys 280 285 290 Thr Tyr His Phe Pro Lys Thr Val Thr Gin Ser Leu Lys Lys Thr 295 300 305 lie Arg Phe Leu His Ser Phe Thr Met Tyr Lys Leu Tyr Gin Lys 310 315 320 This paper is in accordance with the Chinese National Standard (CNS) A4 Specifications (210 X 297 mm) 64 38076 538049 H3 Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economy Leu Phe Leu Glu Met lie Gly Asn Gin Val Gin Ser Val Lys lie 325 330 335 Ser Cys Leu 340 0 46. -A cDNA encoding a protein that inhibits osteoclast formation, characterized by encoding the following amino acid sequences: Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser, 20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 -11 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35 Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80 Arg Cys Pro Asp Gly Phe Phe Ser Asn Glu Thr Ser Ser Lys Ala 85 90 95 Pro Cys Arg Lys His Thr Asn Cys Ser Val Phe Gly Leu Leu Leu 100 105 110 This paper is sized to the Chinese National Standard (CNS ) A4 size (210 X 297 mm) 65 38076 538049 H3 Thr Gin Lys Gly Asn Ala Thr His Asp Asn lie Cys Ser Gly Asm 115 120 125 Ser GIu Ser Thr Gin Lys Cys Gly He Asp Val Thr Leu Cys Glu 130 135 140 Glu Ala Phe Phe A rg Phe Ala Val Pro Thr Lys Phe Thr Pro Asn 145 150 155 Trp Leu Ser Val Leu Val Asp Asn Leu Pro Gly Thr Lys Val Asn 160 165 170 Ala-Glu Ser Val Glu Arg lie Lys Arg Gin His Ser Ser Gin Glu 175 180 185 Gin Thr Phe Gin Lea Leu Lys Leu Trp Lys His Gin Asn Lys Asp 190 195 200 Gin Asp lie Val Lys Lys lie lie Gin Asp lie Asp Leu Cys Glu 205 210 215 Asn Ser Val Gin Arg His lie Gly His Ala Asn Leu Thr Phe Glu 220 225 230 Gin Leu Arg Ser Leu Met Glu Ser Leu Pro Gly Lys Lys Val Gly 235 240 245 Ala Glu Asp lie Glu Lys Thr lie Lys Ala Cys Lys Pro Ser Asp 250 255 260 Gin lie Leu Lys Leu Leu Ser Leu Trp Arg lie Lys Asn Gly Asp Printed by the Employee Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs 265 270 275 Gin Asp Thr Leu Lys Gly Leu Met His Ala Leu Lys His Ser Lys 280 285 290 Thr Tyr His Phe Pro Lys Thr Val Thr Gin Ser Leu Lys Lys Thr 295 300 305 lie Arg Phe Lea His Ser Phe Thr Met Tyr Lys Lea Tyr Gla Lys 310 315 320 This paper size applies to China National Standard (CNS) A4 (210 x 297 mm) ) 66 38076 538049 H3 Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economy π Leu Phe Leu Gla Met lie Gly Asn Gin Val Gin Ser Val Lys lie 325 330 335 Ser Cys Leu 340 0 47. - encodings inhibition cDNA-protein formation of osteoclasts, wherein the cDNA shown below Salt yl sequence: ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 GTGTGCGCCG AATGCAAGGA AGGGCGCTAC CTTGAGATAG AGTTCTGCTT GftAACATAGG 240 AGCTGCCCTC CTGGATTTGG AGTGGTGCAA GCTGGAACCC CAGAGCGAAA TACAGTTTGC 300 AAAAGATGTC CAGATGGGTT CTTCTCAAAT GAGACGTCAT CTAflAGCACC CTGTAGAAAA 360 CSCACAAATT GCAGTGTCTT TGGTCTCCTG CTAACTCAGA AAGGAAATGC AACACACGAC 420 AACATATGTT CCGGAAACAG TGAATCAACT CAAAAATGTG GAATAGATGT TACCCTGTGT 480 GAGGAGGCAT TCTTCAGGTT TGCTGTTCCT ACAAAGTTTA CGCCTAACTG GCTTAGTGTC 540 TTGGTAGACA ATTTGCCTGG CACCAAAGTA AACGCAGAGA GTGTAGAGAG GATAAAACGG 600 CAACACAGCT CACAAGAACA GACTTTCCAG CTGCTGAAGT TATGGAAACA TCAAAACAAA 660 G4CCAAGATA TAGTCAAGAA GATCATCCAA GATATTGACC TCTGTGAAAA CAGCGTGCAG 720 CGGCACATTG GACATGCTAA CCTCACCTTC GAGCAGCTTC GTAGCTTGAT GG AAAGCTTA 780 CCGGGAAAGA AAGTGGGAGC AGAAGACATT GAAAAAACAA TAAAGGCATG CAAACCCAGT 840 GACCAGATCC TGAAGCTGCT CAGTTTGTGG CGAATAAAAA ATGGCGACCA AGACACCTTG 900 AAGGGCCTAA TGCACGCACT AAAGCACTCA AAGACGTACC ACTTTCCCAA AACTGTCACT 960 CAGAGTCTAA AGAAGACCAT CAGGTTCCTT CACAGCTTCA CAATGTACAA ATTGTATCAG 1020 AAGTTATTTT TAGAAATGAT AGGTAACCAG GTCCAATCAG TAAAAATAAG CTGCTTATAA 1080. 4 8. —A protein that inhibits the formation of human osteoclasts and is composed of the following amino acid sequences Nos. 1 to 338, which are characterized by the expression of cDNA in the 47th scope of the patent application: This paper is applicable to China Standard (CNS) Α4 size (210 X 297 mm) 67 38076 538049 H3 Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 -11 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35 Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80 Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Leu Lys 85 90 95 Printed by the Staff Welfare Committee of the Central Bureau of Standards of the Ministry of Economic Affairs This paper is sized to the Chinese National Standard (CNS) A4 (210 X 297 mm) 68 38076 538049 H 3 Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Gly Thr 100 105 110 Pro Glu Arg Asn Thr Val Cys Lys Ser Gly Asn Ser Glu Ser Thr 115 120 125 Gin Lys Cys Gly lie Asp Val Thr Leu Cys Glu Glu Ala Phe Phe 130 135 140 Arg Phe Ala Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val 145 150 155 Leu Val Asp Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val 160 165 170 Glu Arg lie Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe Gin 175 180 185 Leu Leu Lys Leu Trp Lys His Gin Asn Lys Asp Gin Asp lie Val 190 195 200 Lys Lys lie lie Gin Asp lie Asp Leu Cys Glu Asn Ser Val Gin 205 210 215 Arg His lie Gly His Ala Asn Leu Thr Phe Glu Gin Leu Arg Ser 220 225 230 Leu Met Glu Ser Leu Pro Gly Lys Lys Val Gly Ala Glu Asp lie 235 240 245 Glu Lys Thr lie Lys Ala Cys Lys Pro Ser Asp Gin lie Leu Lys 250 255 260 Leu Leu Ser Leu Trp Arg lie Lys Asn Gly Asp Gin Asp Thr Leu 265 270 275 Lys Gly Leu Met His Ala Leu Lys His Ser Lys Thr Tyr His Phe 280 285 290 Pro Lys Thr Val Thr Gin Ser Leu Lys Lys Thr lie Arg Phe Leu 295 300 305 This paper size applies to China National Standard (CNS) A4 (210 x 297 mm) 69 38076 538049 H3 Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economy Ser Phe Thr Met Tyr Lys Leu Tyr Gin Lys Leu Phe Leu Glu 310 315 320 Met lie Gly Asn Gin Val Gin Ser Val Lys lie Ser Cys Leu 325 330 335. 49. A cDNA encoding a protein that inhibits osteoclast formation, characterized by encoding the following amino acid sequence: Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 -11 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35 Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80 Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Leu Lys 85 90 95 This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 70 38076 538049 H3 Central Bureau of Standards, Ministry of Economic Affairs Printed by the Employee Welfare Committee His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Gly Thr 100 105 110 Pro Glu Arg Asn Thr Val Cys Lys Ser Gly Asn Ser Glu Ser Thr 115 120 125 Gin Lys Cys Gly lie Asp Val Thr Leu Cys Glu Glu Ala Phe Phe 130 135 140 Arg Phe Ala Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val 145 150 155 LeuVal Asp Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val 160 165 170 Glu Arg lie Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe Gin 175 180 185 Leu Leu Lys Leu Trp Lys His Gin Asn Lys Asp Gin Asp lie Val 190 195 200 Lys Lys He lie Gin Asp lie Asp Leu Cys Glu Asn Ser Val Gin 205 210 215 Arg His lie Gly His Ala Asn Leu Thr Phe Glu Gin Leu Arg Ser 220 225 230 Leu Met Glu Ser Leu Pro Gly Lys Lys Val Gly Ala Glu Asp lie 235 240 245 Glu Lys Thr lie Lys Ala Cys Lys Pro Ser Asp Gin lie Leu Lys 250 255 260 Leu Leu Ser Leu Trp Arg lie Lys Asn Gly Asp Gin Asp Thr Leu 265 270 275 Lys Gly Leu Met His Ala Leu Lys His Ser Lys Thr Tyr His Phe 280 285 290 Pro Lys Thr Val Thr Gin Ser Leu Lys Lys Thr lie Arg Phe Leu 295 300 305 This paper size applies to Chinese National Standard (CNS) A4 (210 X 297 mm) 71 38076 538049 H3 His Ser Phe Thr Met Tyr Lys Leu Tyr Gin Lys Leu Phe Leu Glu 310 315 320 M et lie Gly Asn Gin Val Gin Ser Val Lys lie Ser Cys Leu 325 330 335. 5 0. - encodings inhibition cDNA-protein formation of osteoclasts, wherein the cDNA shown below Salt yl sequence: ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGC4GGAGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 & TTTGCAAAA GATGTCCAGA TGGGTTCTTC TCAAATGAGA CGTCATCTAA AGCACCCTGT 480 AGAAAACACA CAflATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG AAATGCAACA 540 CACGACAACA TATGTTCCGG AAACAGTGAA TCAACTCAAA AATGTGGAAT AGATATTGAC 600 CTCTGTGAAA ACAGCGTGGA GCGGCACATT GGACATGCTA ACCTCACCTT CGAGCAGCTT 660 CGTAGCTTGA TGGAAAGCTT ACCGGGAAAG AAAGTGGGAG CAGAAGACAT TGAAAAAACA 720 ftTAAAGGCAT GCAftACCCAG TGACCAGATC CTGAA GCTGC TCAGTTTGTG GCGAATAAAA 780 AATGGCGACC AAGACACCTT GAAGGGCCTA ATGCACGCAC TAAAGCACTC AAAGACGTAC 840 CACTTTCCCA AAACTGTCAC TCAGAGTCTA AAGAAGACCA TCAGGTTCATATCCCTCAGTCTCATCACCATCTAGTCACA —A kind of protein that inhibits human osteoclast formation and is composed of the following amino acid sequences Nos. 1 to 305, which are obtained from the cDNA expression of item 50 in the scope of patent application: This paper size applies Chinese national standards ( CNS) A4 size (210 X 297 mm) 72 38076 538049 H3 Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 -11 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35 Val € ys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80 Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Leu Lys 85 90 95 Printed by the Staff Welfare Committee of the Central Bureau of Standards of the Ministry of Economic Affairs This paper is printed in accordance with China National Standard (CNS) A4 (210 X 297 mm) 73 38076 538049 Central Ministry of Economic Affairs Bureau of Standards Printed by the Employee Welfare Committee H3_ His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Gly Thr 100 105 110 Pro Glu Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 115 120 125 Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 130 135 140 Cys Ser Val Phe Gly Leu Leu Leu Thr Gin Lys Gly Asn Ala Thr 145 150 155 His. Asp Asn lie Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Cys 160 165 170 Gly lie Asp lie Asp Leu Cys Glu Asn Ser Val Gin Arg His lie 175 180 185 Gly His Ala Asn Leu Thr Phe Glu Gin Leu Arg Ser Leu Het Glu 190 195 200 Ser Leu Pro Gly Lys Lys Val Gly Ala Glu Asp lie Glu Lys Thr 205 210 215 lie Lys Ala Cys Lys Pro Ser Asp Gin lie Leu Lys Leu Leu Ser 220 225 230 Leu Trp Arg lie Lys Asn Gly Asp Gin Asp Thr Leu Lys Gly Leu 235 240 245 Met His Ala Leu Lys His Ser Lys Thr Tyr His Phe Pro Lys Thr 250 255 260 Val Thr Gin Ser Leu Lys Lys Thr lie Arg Phe Leu His Ser Phe 265 270 275 Thr Met Tyr Lys Leu Tyr Gin Lys Leu Phe Leu Glu Met lie Gly 280 285 290 Asn Gin Val Gin Ser Val Lys lie Ser Cys Leu 295 300 305. 52. —A cDNA encoding a protein that inhibits osteoclast formation. The characteristics of this paper are applicable to the Chinese National Standard (CNS) A4 (210 X 297 mm) 74 38076 538049 _ H3_ is the one encoding the following amino acid sequence: Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pros Lys Tyr Leu His -5 -1 1 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gliv His Cys Thr Ala Lys Trp Lys Thr 25 30 35 Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80 Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Leu Lys 85 90 95 Economy Printed by the Staff Welfare Committee of the Ministry of Standards of the People ’s Republic of China. The paper size is applicable to the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 75 38076 538049 Gly Phe Gly Val Val Gin Ala Gly Thr 100 105 110 Pro GIu Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 115 120 125 Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 130 135 140 Cys Ser Val Phe Gly Leu Leu Leu Thr Gin Lys Gly Asn Ala Thr 145 150 155 His-Asp Asn lie Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Cys 160 165 170 Gly lie Asp lie Asp Leu Cys Glu Asn Ser Val Gin Arg His lie 175 180 185 Gly His Ala Asn Leu Thr Phe Glu Gin Leu Arg Ser Lea Met Glu 190 195 200 Ser Leu Pro Gly Lys Lys Val Gly Ala Glu Asp lie Glu Lys Thr 205 210 215 lie Lys Ala Cys Lys Pro Ser Asp Gin lie Leu Lys Leu Leu Ser 220 225 230 Leu Trp Arg lie Lys Asn Gly Asp Gin Asp Thr Leu Lys Gly Leu 235 240 245 Met His Ala Leu Lys His Ser Lys Thr Tyr His Phe Pro Lys Thr 250 255 260 Val Thr Gin Ser Leu Lys Lys Thr lie Arg Phe Leu His Ser Phe 265 270 275 Thr Met Tyr Lys Leu Tyr Gin Lys Leu Phe Leu Glu Met lie Gly 280 285 290 Asn Gin Val Gin Ser Val Lys lie Ser Cys Leu 295 300 305. 53. —A kind of cDNA encoding a protein that inhibits osteoclast formation. The characteristics of this paper are applicable to the Chinese National Standard (CNS) A4 specification (210 X 297 male f: 38076 538049 _H3_ is the cDNA shown in the following amyloid sequence: ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 GTTTGCAAAA GATGTCCAGA TGGGTTCTTC TCAAATGAGA CGTCATCTAA AGCACCCTGT 480 AGAMACACA CAAATTGCAG TGTCHTGGT CTCCTGCTAA CTCAG / tAAGG AAATGCAACA 540 CACGACAACA TATGTTCCGG AAACAGTGAA TCAACTCAAA AATGTGGAAT AGATGTTACC 600 CTGTGTGAGG AGGCATTCTT CAGGTTTGCT GTTCCTCC TAGCAGTCCAGTAC TAAACG CAGAGAGTGT AGAGAGGATA 720 AAACGGCAAC ACAGCTCACA AGAACAGACT TTCCAGCTGC TGAAGTTATG GAAACATCAA 780 AACAAAGACC AAGATATAGT CAAGAAGATC ATCCAAGACG CACTAAAGCA CTCAAAGACG 840 TACCACTTTC CCAAAACTGT CACTCAGAGT CTAAAGAAGA CCATCAGGTT CCTTCACAGC 900 TTCACAATGT ACAAATTGTA TCAGAAGTTA TTTTTAGAAA TGATAGGTAA CCAGGTCCAA 960 TCAGTAAAAA TAAGCTGCTT ATAA 984 〇54. -A protein that inhibits human osteoclast formation and is composed of the following amino acid sequences Nos. 1 to 3 06, which are derived from the cDNA expression of the 53rd patent application: Employee Benefits of the Central Standards Bureau of the Ministry of Economic Affairs The paper size printed by the committee applies the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 77 38076 538049 H3 Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 -11 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35 Val. Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80 Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Leu Lys 85 90 95 His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Gly Thr 100 105 110 Pro Glu Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 115 120 125 Printed by the Staff Welfare Committee of the Central Bureau of Standards, Ministry of Economic Affairs This paper is sized for the Chinese National Standard (CNS) A4 (210 X 297 mm) 78 38076 538049 __ H3__ Ser Asm Glu Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 130 135 140 Cys Ser Val Phe Gly Leu Lea Leu Thr Gin Lys Gly Asn Ala Thr 145 150 155 His Asp Asn lie Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Cys 160 165 170 Gly lie Asp Val Thr Leu Cys Glu Glu Ala Phe Phe Arg Phe Ala 175 180 185 Val- Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val Leu Val Asp 190 195 200 Asn Leu Pro Gly Thr Lys Val Asn Ala Glu S er Val Glu Arg lie 205 210 215 Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe Gin Leu Leu Lys 220 225 230 Leu Trp Lys His Gin Asn Lys Asp Gin Asp lie Val Lys Lys lie 235 240 245 lie Gin Asp Ala Leu Lys His Ser Lys Thr Tyr Tyr His Phe Pro Lys 250 255 260 Thr Val Thr Gin Ser Leu Lys Lys Thr lie Arg Phe Leu His Ser 265 270 275 Phe Thr Met Tyr Lys Leu Tyr Gin Lys Leu Phe Leu Glu Met lie Central Bureau of Standards, Ministry of Economy Printed by the Employee Welfare Committee 280 285 290 Gly Asn Gin Val Gin Ser Val Lys lie Ser Cys Leu 295 300 305 o 55. —A cDNA encoding a protein that inhibits osteoclast formation, which is characterized by encoding the following amino acid sequence: This paper size applies the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 79 38076 538049 H3 Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 A 1 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr * 25 30 35 Val Cys Ala Fro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80 Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Leu Lys 85 90 95 His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Gly Thr 100 105 110 Pro Glu Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 115 120 125 China National Standard (CNS) A4 specification (210 X 297 mm) 80 38076 538049 H3 Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 130 135 140 Cys Ser Val Phe Gly Leu Leu Leu Thr Gin Lys Gly Asn Ala Thr 145 150 155 His Asp Asn lie Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Cys 160 165 170 Gly lie Asp Val Thr Leu Cys Glu Glu Ala Phe Phe Arg Phe Ala 175 180 185 Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val Leu Val Asp 190 195 200 Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg lie 205 210 215 Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe Gin Leu Leu Lys 220 225 230 Leu Trp Lys His Gin Asn Lys Asp Gin Asp lie Val Lys Lys lie 235 240 245 lie Gin Asp Ala Leu Lys His Ser Lys Thr Tyr His Phe Pro Lys 250 255 260 Thr Val Thr Gin Ser Leu Lys Lys Thr lie Arg Phe Leu His Ser 265 270 275 Phe Thr Met Tyr Lys Leu Tyr Gin Lys Leu Phe Leu Glu Met lie Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs 280 285 290 Gly Asn Gin Val Gin Ser Val Lys lie Ser Cys Leu 295 300 305. 5 6. —A cDNA encoding a protein that inhibits the formation of osteoclasts, which is characterized by the following cDNA sequence: This paper is in accordance with the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 81 38076 538049 ____H3_ ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTftC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 GTTTGCAAAA GATGTCCAGA TGGGTTCTTC TCAAATGAGA CGTCATCTAA AGCACCCTGT 480 AGAAAACACA CAAATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG AAATGCAACA 540 CACGACAACA TATGTTCCGG AAACAGTGAA TCAACTCAAA AATGTGGAAT AGATGTTACC 600 CTGTGTGAGG AGGCATTCTT CAGGTTTGCT GTTCCTACTA AGGGC GCCTGGCACC AAAGTAAACG CAGAGAGTGT AGAGAGGATA 720 AAACGGCAAC ACAGCTCACft AGAACAGACT TTCCAGCTGC TGAAGTTATG GAAACATCAA 780 AACAAAGACC AAGATATAGT CAAGAAGATC ATCCAAGATA TTGACCTCTG TGAAAACAGC 840 GTGCAGCGGC ACATTGGACfl TGCTAACCTC ACCTTCGAGC AGCTTCGTAG CTTGATGGAA 900 AGCTTACCGG GAAAGAAAGT GGGAGCAGAA GACATTGAAA AAACAATAAA GGCATGCAAA 960 CCCAGTGACC AGATCCTGAA GCTGCTCAGT TTGTGGCGAA TAAAAAATGG CGACCaAGAC 1020 ACCTTGAAGG GCCTAATGCA CGCACTAAAG CACTCAAAGA CGTACCACTT TCCCAAAACT 1080 GTCACTCAGA GTCTAAAGAA GACCATCAGG TTCCTTCACA GCTTCACAAT GTACAAATTG 1140 TATCAGAAGT TATHTTAGA AATGATAGGT AACCAGGTCC AATCAGTAAA AATAAGCTAA 1200. 5 7. —A protein that inhibits human osteoclast formation and is composed of the following amino acid sequences Nos. 1 to 378, which is characterized by being obtained by a patent applicant and presenting the item of AND C in the central section of the Ministry of Economy Printed by the Staff Welfare Committee of the Bureau of Standards. The paper size applies to the Chinese National Standard (CNS) A4 (210 X 297 mm) 82 38076 538049 H3 Printed by the Staff Welfare Committee of the Central Bureau of Standards of the Ministry of Economy. Met Asn Asn Len Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15, 10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 -1 1 5 Tyr Asp Glu Glu TGlu Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35 Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80 Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Leu Lys 85 90 95 His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Gly Thr 100 105 110 Pro Glu Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 115 120 125 Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 130 135 140 Cys Ser Val Phe Gly Leu Leu Leu Thr Gin Lys Gly Asn Ala Thr 145 150 155 This paper size applies to Chinese National Standard (CNS) A4 (210 X 297 mm) 83 38076 538049 H3 Printed by His Welfare Committee of the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs His Asp Asn lie Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Cys 160 165 170 Gly lie Asp Val Thr Leu Cys Glu Glu Ala Phe Phe Arg Phe Ala 175 180 185 Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val Leu Val Asp 190 195 200 Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg lie 205 210 215 Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe Gin Leu Leu Lys 220 225 230 Leu Trp Lys His Gin Asn Lys Asp Gin Asp lie Val Lys Lys lie 235 240 245 lie Gin Asp lie Asp Leu Cys Glu Asn Ser Val Gin Arg His lie 250 255 260 Gly His Ala Asn Leu Thr Phe Glu Gin Leu Arg Ser Leu Met Glu 265 270 275 * Ser Leu Pro Gly Lys Lys Val Gly Ala Glu Asp lie Glu Lys Thr 280 285 290 lie Lys Ala Cys Lys Pro Ser Asp Gin lie Leu Lys Leu Leu Ser 295 300 305 Leu Trp Arg lie Lys Asn Gly Asp Gin Asp Thr Leu Lys Gly Leu 310 315 320 Met His Ala Leu Lys His Ser Lys Thr Tyr His Phe Pro Lys Thr 325 330 335 Val Thr Gin Ser Leu Lys Lys Thr lie Arg Phe Leu His Ser Phe 340 345 350 Thr Met Tyr Lys Leu Tyr Gin Lys Leu Phe Leu Glu Met lie Gly 355 360 365 Asn Gin Val Gin Ser Val Lys lie Ser 370 375 〇 5 8. —A cDNA encoding a protein that inhibits the formation of osteoclasts. The characteristics of this paper are in accordance with the Chinese National Standard (CNS) Standard 4 (210 X 297 mm) 84 38076 538049 Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs_H3_ Those who encode the following amino acid sequences: Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 -1 1 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35 Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80 Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Leu Lys 85 90 95 His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Gly Thr 100 105 110 Pro Glu Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 115 120 125 Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 130 135 140 Cys Ser Val Phe Gly Lea Leu Leu Thr Gin Lys Gly Asn Ala Thr 145 150 155 This paper size applies to China National Standard (CNS) A4 specification (210 X 297 mm) 85 38076 538049 H3 Printed by the Staff Welfare Committee of the Central Bureau of Standards, Ministry of Economic Affairs His Asp Asn lie Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Cys 160 165 170 Gly lie Asp Val Thr Leu Cys Glu Glu Ala Phe Phe Arg Phe Ala 175 180 185 Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val Leu Val Asp 190 195 200 Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg lie 205 210 215 Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe Gin Leu Leu Lys 220 225 230 Leu Trp Lys His Gin Asn Lys Asp- Gin Asp lie Val Lys Lys lie 235 240 245 lie Gin Asp lie Asp Leu Cys Glu Asn Ser Val Gin Arg His lie 250 255 260 Gly His Ala Asn Leu Thr Phe Glu Gin Leu Arg Ser Leu Met Glu 265 270 275 Ser Lea Pro Gly Lys Lys Val Gly Ala Glu Asp lie Glu Lys Thr 280 285 290 lie Lys Ala Cys Lys Pro Ser Asp Gin lie Leu Lys Leu Leu Ser 295 300 305 Leu Trp Arg lie Lys Asn Gly Asp Gin Asp Thr Leu Lys Gly Leu 310 315 320 Met His Ala Leu Lys His Ser Lys Thr Tyr His Phe Pro Lys Thr 325 330 335 Val Thr Gin Ser Leu Lys Lys Thr lie Arg Phe Lea His Ser Phe 340 345 350 Thr Met Tyr Lys Leu Tyr Gin Lys Leu Phe Leu Glu Met lie Gly 355 360 365 Asn Gin Val Gin Ser Val Lys lie Ser 370 375 〇59. —A cDNA encoding a protein that inhibits osteoclast formation. The characteristics of this paper are in accordance with Chinese National Standard (CNS) A4 (210 X 297 mm). 86 38076 538049 _H3_ is the cDNA shown in the following amyloid sequence: ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 GTTTGCAAAA GATGTCCAGA TGGGTTCTTC TCAAATGAGA CGTCATCTAA AGCACCCTGT 480 AGAAAACACA CAAATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG AAATGCAACA 540 CACGACAACA TATGTTCCGG AAACAGTGAA TCAACTCAAA AATGTGGAAT AGATGTTCATC CTCTGTGTGAGG AGGCATTCTT CAGGTTTGCT TACTCGCTGTCT GGCACC AAAGTAAACG CAGAGAGTGT AGAGAGGATA 720 AAACGGCAAC ACAGCTCACA AGAACAGACT TTCCAGCTGC TGAAGTTATG GAAACATCAA 780 AACAAAGACC AAGATATAGT CAAGAAGATC ATCCAAGATA TTGACCTCTG TGAAAACAGC 840 GTGCAGCGGC ACATTGGACA TGCTAACCTC ACCTTCGAGC AGCTTCGTAG CTTGATGGAA 900 AGCTTACCGG GAAAGAAAGT GGGAGCAGAA GACATTGAAA AAACAATAAA GGCATGCAAA 960 CCCAGTGACC AGATCCTGAA GCTGCTCAGT TTGTGGCGAA TAAAAAATGG CGACCAAGAC 1020 ACCTTGAAGG GCCTAATGCA CGCACTAAAG CACTGA 1056 060 · - kind of suppression The human osteoclast-forming protein consisting of the following amino acid sequences Nos. 1 to 3 30 is derived from the expression of cDNA in item 59 of the scope of patent application: Staff Benefit Kit of the Central Standards Bureau of the Ministry of Economic Affairs The printed paper size is in accordance with Chinese National Standard (CNS) A4 (210 297 mm) 87 38076 538049 H3 Met Asn Asn Leu Leu Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 -11 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Ly s Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35 Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80 Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Leu Lys 85 90 95 His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Gly Thr 100 105 110 Printed by the Staff Welfare Committee of the Central Bureau of Standards of the Ministry of Economic Affairs Printed on a paper size applicable to the Chinese National Standard (CNS) A4 (210 X 297 mm) 88 380 邛 538049 H3 Printed by Pro Glu Arg, Member of the Welfare Committee of the Central Bureau of Standards of the Ministry of Economic Affairs Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 115 120 125 Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 130 135 140 Cys Ser Val Phe Gly Leu Leu Leu Thr Gin Lys Gly Asn Ala Thr 145 150 155 His Asp Asn lie Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Cys 160 165 170 Gly lie Asp Val Thr Leu Cys Glu Glu Ala Phe Phe Arg Phe Ala 175 180 185 Val Pro Thr Lys Phe Thr Pro Asn Trp Le u Ser Val Leu Val Asp 190 195 200 Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg lie 205 210 215 Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe Gin Leu Leu Lys 220 225 230 Leu Trp Lys His Gin Asn Lys Asp Gin Asp lie Val Lys Lys lie 235 240 245 lie Gin Asp lie Asp Leu Cys Glu Asn Ser Val Gin Arg His lie 250 255 260 Gly His Ala Asn Leu Thr Phe Glu Gin Leu Arg Ser Leu Met Glu 265 270 275 Ser Leu Pro Gly Lys Lys Val Gly Ala Glu Asp lie Glu Lys Thr 280 285 290 lie Lys Ala Cys Lys Pro Ser Asp Gin He Leu Lys Leu Leu Ser 295 300 305 Leu Trp Arg lie Lys Asn Gly Asp Gin Asp Thr Leu Lys Gly Leu 310 315 320 Met His Ala Leu Lys His 325 330 6 1. — A cDNA encoding a protein that inhibits osteoclast formation. The characteristics of this paper are applicable to the Chinese National Standard (CNS) A4 (210 X 297 mm) 89 38076 538049 H3 is the one encoding the following amino acid sequence: Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 -11 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35 Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80 Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Gla Phe Cys Leu Lys 85 90 95 His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Gly Thr 100 105 110 Printed by the Staff Welfare Committee of the Central Bureau of Standards, Ministry of Economic Affairs This paper is scaled to Chinese National Standard I (CNS) A4 (210 X 297 mm) 90 38076 538049 H3 Ministry of Economic Affairs Printed by the Staff Welfare Committee of the Central Bureau of Standards Pro Glu Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 115 120 125 Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 130 135 140 Cys Ser Val Phe Gly Leu Leu Leu Thr Gin Lys Gly Asn Ala Thr 145 150 155 His Asp Asn lie Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Cys 160 165 170 Gly lie Asp Val Thr Leu Cys Glu Glu Ala Phe Phe Arg Phe Ala 175 180 185 Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val Leu Val Asp 190 195 200 Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg lie 205 210 215 Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe Gin Leu Leu Lys 220 225 230 Leu Trp Lys His Gin Asn Lys Asp Gin Asp lie Val Lys Lys lie 235 240 245 lie Gin Asp lie Asp Leu Cys Glu Asn Ser Val Gin Arg His lie 250 255 260 Gly His Ala Asn Leu Thr Phe Glu Gin Leu Arg Ser Leu Met Glu 265 270 275 Ser Leu Pro Gly Lys Lys Val Gly Ala Glu Asp lie Glu Lys Thr 280 285 290 lie Lys Ala Cys Lys Pro Ser Asp Gin He Leu Lys Leu Lea Ser 295 300 305 Leu Trp Arg lie Lys A sn Gly Asp Gin Asp Thr Leu Lys Gly Leu 310 315 320 Met His Ala Leu Lys His 325 330 0 6 2. —A type of cDNA encoding a protein that inhibits osteoclast formation. The characteristics of this paper are applicable to the Chinese National Standard (CNS) A4 (210 X 297 mm) 91 538049 ___ H3_ is the cDNA shown in the following amyloid sequence: ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 GTTTGCAAAA GATGTCCAGA TGGGTTCTTC TCAAATGAGA CGTCATCTAA AGCACCCTGT 480 AGAAAACACA CAAATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG AAATGCAACA 540 CACGACAACA TATGTTCCGG AAACAGTGAA TCAACTCAAA AATGTGGAAT AGATGTTCATC CTCTGTGTGAGG AGGCATTCTT CAGGTTTGCT TACTCGCTGTCT C AAAGTAAACG CAGAGAGTGT AGAGAGGATA 720 AAACGGCAAC ACAGCTCACA AGAACAGACT TTCCAGCTGC TGAAGTTATG GAAACATCAA 780 AACAAAGACC AAGATATAGT CAAGAAGATC ATCCAATGA 819. 63. -A protein that inhibits human osteoclast formation and is composed of the following amino acid sequences Nos. 1 to 251, which are obtained from the cDNA expression of the 62nd patent application scope: Staff Welfare Committee of the Central Standards Bureau, Ministry of Economic Affairs Printed paper sizes are in accordance with Chinese National Standards (CNS) A4 (210 X 297 mm) 92 38076 538049 H3 Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 -11 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35 Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80 Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Leu Lys 85 90 95 His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Gly Thr 100 105 110 Staff Welfare Committee, Central Standards Bureau, Ministry of Economic Affairs Print This paper size applies to Chinese National Standard (CNS) A4 (210 X 297 mm) 93 38076 538049 H3 Pro Glu Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 115 120 125 Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 130 135 140 Cys Ser Val Phe Gly Leu Leu Leu Thr Gin Lys Gly Asn Ala Thr 145 150 155 His Asp Asn lie Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Cys 160 165 170 Gly lie Asp Val Thr Leu Cys Glu Glu Ala Phe Phe Arg Phe Ala 175 180 185 Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val Leu Val Asp 190 195 200 Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg lie 205 210 215 Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe Gin Leu Leu Lys 220 225 230 Leu Trp Lys His Gin Asn Lys Asp Gin Asp lie Val Lys Lys lie 235 240 245 lie Gin 250 Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs 64. —A cDNA encoding a protein that inhibits osteoclast formation, which is characterized by encoding the following amino acid sequence: This paper size is applicable to the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 9 1038076 538049 H3 Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 -11 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala -Lys Trp Lys Thr 25 30 35 Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys TO 75 80 Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Leu Lys 85 90 95 His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Gly Thr 100 105 110 Printed by the Staff Welfare Committee of the Central Bureau of Standards, Ministry of Economic Affairs This paper is scaled to the Chinese National Standard (CNS) A4 (210 X 297 mm) 95 38076 538049 H3 Economy Printed by the Staff Welfare Committee of the Central Bureau of Standards Pro Glu Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 115 120 125 Ser Asn Gla Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 130 135 140 Cys Ser Val Phe Gly Leu Leu Leu Thr Gin Lys Gly Asn Ala Thr 145 150 155 His Asp Asn lie Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Cys 160 165 170 Gly He Asp Val Thr Leu Cys Glu Glu Ala Phe Phe Arg Phe Ala 175 180 185 Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val Leu Val Asp 190 195 200 Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg lie 205 210 215 Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe Gin Leu Leu Lys 220 225 230 Leu Trp Lys His Gin Asn Lys Asp Gin Asp lie Val Lys Lys lie 235 240 245 lie Gin 250. 65. — A CDNA encoding a protein that inhibits osteoclast formation, characterized by the following cDNA sequence: This paper is sized for the Chinese National Standard (CNS) A4 (21 | 0 X 297 mm) 96 38076 538049 H3 ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC Γ80 GTGTGCGCCC CTTGCCCTGA CCACTACTflC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGG9GCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 GTTTGCAAAA GATGTCCflGA TGGGTTCTTC TCAAATGAGA CGTCATCTAA AGCACCCTGT 480 AGAAAACACA CAAATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG AAATGCAACA 540 CACGACAACA TATGTTCCGG AAACAGTGAJi TCA4CTCAAA AATGTGGAAT ATGA 594. 6 6. —A protein that inhibits human osteoclast formation and is composed of the following amino acid sequences Nos. 1 to 176, which are obtained from the cDNA expression of the 65th patent application scope: Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs Printed paper size applies Chinese National Standard (CNS) A4 (210 X 297 mm) 97 38076 538049 Printed by the Staff Welfare Committee of the Central Bureau of Standards, Ministry of Economic Affairs_H3_ Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 -11 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35 Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn ftrg Val Cys 70 75 80 Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Leu Lys 85 90 95 His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Gly Thr 100 105 110 Pro Glu Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 115 120 125 Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 130 135 140 Cys Ser Val Phe Gly Leu Leu Leu Thr Gin Lys Gly Asn Ala Thr 145 150 155 His Asp Asn lie Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Cys 160 165 170 Gly lie Π5. 67 · —A cDNA encoding a protein that inhibits the formation of osteoclasts. The characteristics of this paper are in accordance with Chinese National Standard (CNS) A4 (210 X 297 mm) 98 38076 538049 H3 Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs For encoding the following amino acid sequences: Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 -11 5 Tyr Asp Glu Gla Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35 Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80 Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Leu Lys 85 90 95 His Arg Ser Cys Pro Fro Gly Phe Gly Val Val Gin Ala Gly Thr 100 105 110 Pro Glu Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 115 120 125 Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 130 135 140 Cys Ser Val Phe Gly Leu Leu Leu Thr Gin Lys Gly Asn Ala Thr 145 150 155 His Asp Asn lie Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Cys 160 165 170 Gly lie 175. 6 8. — A cDNA encoding a protein that inhibits osteoclast formation, which is characterized by the following cDNA sequence: This paper size applies Chinese National Standard (CNS) A4 specifications (210 X 297 mm) 99 38076 538049 H3 ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTCT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCft AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTiCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 GTTTGCAAftT GA 432 〇6 9. -A protein that inhibits human osteoclast formation and consists of the following amino acid sequences Nos. 1 to 122, which is obtained from the cDNA expression of the 68th patent application scope: Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs Printed paper sizes are in accordance with Chinese National Standard (CNS) A4 (210 x 297 mm) 100 38076 538049 _H3_ Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His * 5 -1 1 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35 Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80 Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Leu Lys 85 90 95 His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Gly Thr 100 105 110 Pro Glu Arg Asn Thr Val Cys Lys 115 120 o 70. —CDNA encoding a protein that inhibits the formation of osteoclasts, which is characterized by the printed sequence of acid amines printed by the Employee Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs. The code below is based on Chinese paper standard (CNS) A4 (210 X 297 mm) 38076 538049 Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs _____H3_ Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 -1 1 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35 Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Tbr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80 Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Leu Lys 85 90 95 His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Gly Thr 100 105 no Pro Glu Arg Asn Thr Val Cys Lys 115 120 o 71. - encodings inhibition cDNA-protein formation of osteoclasts, wherein the cDNA shown below Salt yl sequence: ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG A 321. 72. — A species that inhibits human osteoclast formation and is composed of the following amino acid sequences. The first paper size applies the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 1 2 38076 538049 __H3_ to 85 amino acids The protein is obtained from the cDNA expression of item 71 in the scope of patent application: Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 1 1 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35 Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80 Glu 85 07 3. — A cDNA encoding a protein that inhibits osteoclast formation, characterized by encoding the following amino acid sequence: Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs This paper is in accordance with the Chinese National Standard (CNS) A4 (210 X 297) Mm) 103 38076 538049 H3 Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 -11 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35 Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80 Glu 85 0 74 The CDNA of the formed protein is characterized by the following cDNA sequence: Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs This paper is in accordance with China National Standard (CNS) A4 (210 X 297 mm) 104 38076; 538049 H3 employee welfare committee of Economic Affairs Bureau of Standards printed ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCft TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 GTTTGCAAAA GATGTCCAGA TGGGTTCTTC TCAAATGAGA CGTCATCTAA AGCACCCTGT 480 AGAAAACACA CAAATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG SAATGCftACA 540 CACGACAACA TATGTTCCGG AAACAGTGAA TCAACTCAAA AATGTGGAAT AGATGTTACC 600 CTGTGTGAGG AGGCATTCTT CAGGTTTGCT GTTCCTACAA AGTTTflCGCC TAACTGGCTT 660 AGTGTCTTGG TAGACAATTT GCCTGGCACC AAAGTAAACG CAGAGAGTGT AGAGAGGATA 720 AAACGGCAAC ACAGCTCACA AGAACAGACT TTCCAGCTGC TGAAGTTATG GAAACATCAA 780 AACAAAGACC AAGA TATAGT CAAGAAGATC ATCCAAGATA TTGACCTCTG TGAAAACAGC 840 GTGCAGCGGC ACATTGGACA TGCTAACCTC ACCTTCGAGC AGCTTCGTAG CTTGATGGAA 900 AGCTTACCGG GAAAGAAAGT GGGAGCAGAA GACATTGAAA AAACAATAAA GGCATGCAAA 960 CCCAGTGACC AGATCCTGAA GCTGCTCAGT TTGTGGCGAA TAAAAAATGG CGACCAAGAC 1020 ACCTTGAAGG GCCTAATGCA CGCACTAAAG CACTCAAAGA CGTACCACTT TCCCAAAACT 1080 GTCACTCAGA GTCTAAAGAA GACCATCAGG TTCCTTCACA GCTTCACAAT GTACAAATTG 1140 TATCAGAAGT TATTTTTAGA AATGATAGGT AACCTAGTCT AG 1182. 7 5. —A kind of protein that inhibits human osteoclast formation and consists of the following amino acid sequences Nos. 1 to 3 72 and is derived from the cDNA expression of item 74 of the patent application scope: The paper size applies to Chinese national standards (CNS) A4 size (210 X 297 mm) 105 38076 538049 H3 Printed by Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His ~ 5 -1 1 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35 Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 * Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80 Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Leu Lys 85 90 95 His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Gly Thr 100 105 110 Pro Glu Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 115 120 125 Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 130 135 140 This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 106 38076 538049 H3 Cys Ser Val Phe Gly Leu Leu Leu Thr Gin Lys Gly Asn Ala Thr 145 150 155 His Asp Asn lie Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Cys 160 165 170 Gly lie Asp Val Thr Leu Cys Glu Glu Ala Phe Phe Arg Phe Ala 175 180 185 Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val Leu Val Asp 190 195 200 Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg lie 205 210 215 Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe Gin Leu Leu Lys 220 225 230 Leu Trp Lys His Gin Asn Lys Asp Gin Asp lie Val Lys Lys lie 235 240 245 lie Gin Asp lie Asp Leu Cys Glu Asn Ser Val Gin Arg His lie 250 255 260 Gly His Ala Asn Leu Thr Phe Glu Gin Leu Arg Ser Leu Met Glu 265 270 275 Ser Leu Pro Gly Lys Lys Val Gly Ala Glu Asp lie Glu Lys Thr 280 285 290 lie Lys Ala Cys Lys Pro Ser Asp Gin lie Leu Lys Leu Leu Ser Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs 295 300 305 Leu Trp Arg lie Lys Asn Gly Asp Gin Asp Thr Leu Lys Gly Leu 310 315 320 Met His Ala Leu Lys His Ser Lys Thr Tyr His Phe Pro Lys Thr 325 330 335 Val Thr Gin Ser Leu Lys Lys Thr lie Arg Phe Leu His Ser Phe 340 345 350 This paper size applies to Chinese National Standard (CNS) A4 (210 X 297 mm) 107 38076 538049 H3 Thr Met Tyr Lys Leu Tyr Gin Lys Leu Phe Leu Glu Met lie Gly 355 360 365 Asn Leu Val 370 o 7 6. CDNA encoding a protein that inhibits osteoclast formation, characterized by the following amino acid sequence: Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 -11 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35 Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 * Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80 Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Leu Lys Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs 85 90 95 His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Gly Thr 100 105 110 Pro Glu Arg Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 115 120 125 Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 130 135 140 This paper size applies to Chinese national standards (CNS ) A4 size (210 x 297 mm) 108 38076 538049 H3 Cys Ser Val Phe Gly Leu Leu Leu Thr Gin Lys Gly Asn Ala Thr 145 150 155 His Asp Asn lie Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Cys 160 165 170 Gly lie Asp Val Thr Leu Cys Glu Glu Ala Phe Phe Arg Phe Ala 175 180 185 Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val Leu Val Asp 190 195 200 Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg lie 205 210 215 Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe Gin Leu Leu Lys 220 225 230 Leu Trp Lys His Gin Asn Lys Asp Gin Asp lie Val Lys Lys lie 235 240 245 lie Gin Asp lie Asp Leu Cys Glu Asn Ser Val Gin Arg His lie 250 255 260 Gly His Ala Asn Leu Thr Phe Glu Gin Leu Arg Ser Leu Met Glu 265 270 275 Ser Leu Pro Gly Lys Lys Val Gly Ala Glu Asp lie Glu Lys Thr 280 285 290 employee Printed by Welfare Committee lie Lys Ala Cys Lys Pro Ser Asp Gin lie Leu Lys Leu Leu Ser 295 300 305 Leu Trp Arg lie Lys Asn Gly Asp Gin Asp Thr Leu Lys Gly Leu 310 315 320 Me t His Ala Leu Lys His Ser Lys Thr Tyr His Phe Pro Lys Thr 325 330 335 Val Thr Gin Ser Leu Lys Lys Thr lie Arg Phe Leu His Ser Phe 340 345 350 This paper is sized for China National Standard (CNS) A4 specifications (210 X 297 mm) 109 38076 538049 H3 Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economy Thr Met Tyr Lys Leu Tyr Gin Lys Leu Phe Leu Glu Met lie Gly355 360 365 Asn Leu Val370 o77 · —a code that inhibits osteoclast formation cDNA-protein, wherein the following Salt base sequence of the cDNA as shown: ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACftCCAG TGACGAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 GTTTGCAAAA GATGTC CAGA TGGGTTCTTC TCAAATGAGS CGTCATCTAA AGCACCCTGT 480 AGAAAACACA CAAATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG AAATGCAACA 540 CACGACAACA TATGTTCCGG AAACAGTGAA TCAACTCAAA AATGTGGAAT AGATGTTACC 600 CTGTGTGAGG AGGCATTCTT CAGGTTTGCT GTTCCTACAA AGTTTACGCC TAACTGGCTT 660 AGTGTCTTGG TAGACAATTT GCCTGGCACC AAAGTAAACG CAGAGAGTGT AGAGAGGATA 720 AAACGGCAAC ACAGCTCACA AGAACAGACT TTCCAGCTGC TGAAGTTATG GAAACATCAA 780 AACAAAGACC AAGATATAGT CAAGAAGATC ATCCAAGATA TTGACCTCTG TGAAAACAGC 840 GTGCAGCGGC ACATTGGACA TGCTAACCTC ACCTTCGAGC AGCTTCGTAG CTTGATGGAA 900 AGCTTACCGG GAAAGAAAGT GGGAGCAGAA GACATTGAAA ΑΑΑΟΑΑΤΑΑΛ GGCTAGTCTA 960 GACTAG 966. 78 · —A protein that inhibits human osteoclast formation and is composed of the following amino acid sequences Nos. 1 to 300, which are derived from the cDNA expression of item 77 of the scope of patent application: This paper is applicable to China Standard (CNS) A4 size (210 X 297 mm) 110 38076 538049 H3 Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 -11 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35 Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80 Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Leu Lys 85 90 95 Printed by the Staff Welfare Committee of the Central Bureau of Standards of the Ministry of Economic Affairs This paper applies Chinese national standard (CNS) A4 (210 X 297 mm) 111 38076 538049 H3 His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Gly Thr 100 105 110 Pro Glu Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 115 120 125 Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 130 135 140 Cys Ser Val Phe Gly Leu Leu Leu Thr Gin Lys Gly Asn Ala Thr 145 150 155 His Asp Asn lie Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Cys 160 165 170 Gly lie Asp Val Thr Leu Cys Glu Glu Ala Phe Phe Arg Phe Ala 175 180 185 Val Pro Thr Lys Phe Thr Pro ftsn Trp Lea Ser Val Leu Val Asp 190 195 200 Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg lie 205 210 215 Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe Gin Leu Leu Lys 220 225 230 Leu Trp Lys His Gin Asn Lys Asp Gin Asp lie Val Lys Lys lie 235 240 245 lie Gin Asp lie Asp Leu Cys Glu Asn Ser Val Gin Arg His lie Printed by the Staff Welfare Committee of the Central Standards Bureau, Ministry of Economic Affairs 250 255 260 Gly His Ala Asn Leu Thr Phe Glu Gin Leu Arg Ser Leu Met Glu 265 270 275 Ser Leu Pro Gly Lys Lys Val Gly Ala Glu Asp lie Glu Lys Thr 280 285 290 He Lys Ala Ser Leu Asp 295 300 0 7 9. —A cDNA encoding a protein that inhibits osteoclast formation. The characteristics of this paper are applicable to Chinese National Standard (CNS) A4 (210 X 297 mm) 112 38076 538049 _ H3_ are those encoding the following amino acid sequences: Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser, -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pros Lys Tyr Leu His -5 -11 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Lea Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35 Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80 Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Leu Lys 85 90 95 Central Ministry of Economic Affairs Printed by the Staff Welfare Committee of the Bureau of Standards. The paper size is applicable to Chinese National Standard (CNS) A4 specifications (210 X 297 public love) 113 38076 538049 H3 His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Gly Thr 100 105 110 Pro Gl u Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 115 120 125 Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 130 135 140 Cys Ser Val Phe Gly Leu Leu Leu Thr Gin Lys Gly Asn Ala Thr 145 150 155 His Asp Asn lie Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Cys 160 165 170 Gly lie Asp Val Thr Leu Cys Glu Glu Ala Phe Phe Arg Phe Ala 175 180 185 Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val Leu Val Asp 190 195 200 Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg lie 205 210 215 Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe Gin Leu Leu Lys 220 225 230 Leu Trp Lys His Gin Asn Lys Asp Gin Asp lie Val Lys Lys lie 235 240 245 lie Gin Asp lie Asp Leu Cys Glu Asn Ser Val Gin Arg His lie Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs 250 255 260 Gly His Ala Asn Leu Thr Phe Glu Gin Leu Arg Ser Leu Met Glu 265 270 275 Ser Leu Pro Gly Lys Lys Val Gly Ala Glu Asp lie Glu Lys Thr 280 285 290 lie Lys Ala Ser Leu Asp 295 300. 80. —A type of cDNA encoding a protein that inhibits osteoclast formation. The characteristics of this paper are in accordance with Chinese National Standard (CNS) A4 (210 X 297 mm) 114 38076 538049 Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs H3_ • 为The following Salt base sequence of the cDNA as shown: ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGCAAA GTGGAAGACC 180 GTGTGCGCCC CTTGCCCTGA CCACTACTAC ACAGACAGCT GGCACACCAG TGACGAGTGT 240 CTATACTGCA GCCCCGTGTG CAAGGAGCTG CAGTACGTCA AGCAGGAGTG CAATCGCACC 300 CACAACCGCG TGTGCGAATG CAAGGAAGGG CGCTACCTTG AGATAGAGTT CTGCTTGAAA 360 CATAGGAGCT GCCCTCCTGG ATTTGGAGTG GTGCAAGCTG GAACCCCAGA GCGAAATACA 420 GTTTGCAAAA GATGTCCAGA TGGGTTCTTC TCAAATGAGA CGTCATCTAA AGCACCCTGT 480 AGAAMCACA CAAATTGCAG TGTCTTTGGT CTCCTGCTAA CTCAGAAAGG AAATGCAACA 540 CATG. 8 1. -A protein that inhibits human osteoclast formation and is composed of the following amino acid sequences Nos. 1 to 166, which are obtained from the cDNA expression of the patent application No. 80: Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr iGln Glu Thr Phe Pro Pro Lys Tyr Leu His -5 -1 1 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35 Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp fiis 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cvs This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 115 38076 538049 H3 70 75 80 Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Leu Lys 85 90 95 His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Gly Thr 100 105 110 Pro Glu Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 115 120 125 Ser Asn Glu Thr Ser Ser Lys A la Pro Cys Arg Lys Bis Thr Asn 130 135 140 Cys Ser Val Phe Gly Leu Leu Leu Thr Gin Lys Gly Asn Ala Thr 145 150 155 His Asp Asn lie Cys Ser Gly 160 165 166 82 · —a code that inhibits osteoclast formation The CDNA of a protein is characterized by encoding the following amino acid sequence:

Printed by the Staff Welfare Committee of the Central Bureau of Standards of the Ministry of Economic Affairs. The paper size is applicable to the Chinese National Standard (CNS) A4 (210 X 297 mm) 116 38076 538049 Printed by the Staff Welfare Committee of the Central Bureau of Standards of the Ministry of Economics Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 -1 1 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35 Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80 Glu Cys Lys Glu Gly Arg Tyr Leu Glu He Glu Phe Cys Leu Lys 85 90 95 His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Gly Thr 100 105 110 Pro Glu Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 115 120 125 Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 130 135 140 Cys Ser Val Phe Gl y Leu Leu Leu Thr Gin Lys Gly Asn Ala Thr 145 150 155 His Asp Asn lie Cys Ser Gly 160 165 166. 83 · —CDNA encoding a protein that inhibits osteoclast formation, which is characterized by the following cDNA sequence: $ Paper size applies to Chinese National Standard (CNS) A4 (210 x 297 mm) 117 38076 538049 H3 ATGAACAACT TGCTGTGCTG CGCGCTCGTG TTTCTGGACA TCTCCATTAA GTGGACCACC 60 CAGGAAACGT TTCCTCCAAA GTACCTTCAT TATGACGAAG AAACCTCTCA TCAGCTGTTG 120 TGTGACAAAT GTCCTCCTGG TACCTACCTA AAACAACACT GTACAGTCCGCCACCCGTGAGAAG180 180 GTGTGCGCCC CTTGCCAGCCAC 84. A protein that inhibits human osteoclast formation and is composed of the following amino acid sequences Nos. 1 to 63, which are obtained from the cDNA expression of the patent application No. 83: Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 -11 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35 Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Leu Val 55 60 0 Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs 8. 5. A cDNA encoding a protein that inhibits osteoclast formation, which is characterized by encoding the following amino acid sequence: This paper size applies the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 118 38076 538049 H3 Printed by Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 -11 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35 Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Leu Val 55 60 o 86. A kind of genomic DNA, which is encoded by the cDNA of the 6th patent application, and is A precursor of a human osteoclast-inhibitory protein encoding an amino acid sequence consisting of amino acids Nos. 21 to 3 80 of the following Sequence Listing No. 5; This paper size applies to Chinese National Standard (CNS) A4 (210 x 297 mm) 119 38076 538049 H3 Met Asn Asn Leu Leu Cys Cys Ala Leu Val Phe Leu Asp lie Ser -20 -15 -10 lie Lys Trp Thr Thr Gin Glu Thr Phe Pro Pro Lys Tyr Leu His -5 -1 1 5 Tyr Asp Glu Glu Thr Ser His Gin Leu Leu Cys Asp Lys Cys Pro 10 15 20 Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala Lys Trp Lys Thr 25 30 35 Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His 40 45 50 Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Lys Gla Leu 55 60 65 Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val Cys 70 75 80 Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Leu Lys 85 90 95 His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala Gly Thr 100 105 110 Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs The paper size of the paper is in accordance with Chinese National Standard (CNS) A4 (210 x 297 mm) 120 38076 538049 _H3 Pro Glu Arg Asn Thr Val Cys Lys Arg Cys Pro Asp Gly Phe Phe 115 120 125 Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys Arg Lys His Thr Asn 130 135 140 Cys Ser Val Phe Gly Leu Leu Leu Thr Gin Lys Gly Asn Ala Thr 145 150 155 His Asp Asn lie Cys Ser Gly Asn Ser Glu Ser Thr Gin Lys Cys 160 165 170 Gly-lie Asp Val Thr Leu Cys Glu Glu Ala Phe Phe Arg Phe Ala 175 180 185 Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val Leu Val Asp 190 195 200 Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg lie 205 210 215 Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe Gin Leu Lea Lys 220 225 230 Leu Trp Lys His Gin Asn Lys Asp Gin Asp lie Val Lys Lys lie 235 240 245 lie Gin Asp lie Asp Leu Cys Glu Asn Ser Val Gin Arg His lie 250 255 260 Gly His Ala Asn Leu Thr Phe Glu Gin Leu Arg Ser Leu Met Glu Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs 265 270 275 Ser Leu Pro Gly Lys Lys Val Gly Ala Glu Asp lie Glu Lys Thr 280 285 290 lie Lys Ala Cys Lys Pro Ser Asp Gin lie Leu Lys Leu Leu Ser 295 300 305 Leu Trp Arg I [e ^ ys Asn Gly Asp Gin Asp Thr Leu Lys Gly Leu 310 315 320 National Standard (CNS) A4 (210 x 297 mm) 121 38076 538049 ___H3_ Met His Ala Leu Lys His Ser Lys Thr Tyr His Phe Pro Lys Thr 325 330 335 Val Thr Gin Ser Leu Lys Lys Thr lie Arg Phe Leu His Ser Phe 340 345 350 Thr Met Tyr Lys Leu Tyr Gin Lys Leu Phe Leu Glu Met lie Gly 355 360 365 Asn Gin Val Gin Ser Val Lys lie Ser Cys Leu 370 375 380. 87. For example, the genomic DNA of the 86th scope of the patent application is shown by the following base sequence: Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs This paper is printed in accordance with the Chinese National Standard (CNS) A4 (210 X 297) PCT) 122 38076 538049 H3 CTGGAGACAT ATAACTTGAA CACTTGGCCC TGATGGGGAA GCAGCTCTGC AGGGACTTTT 60 TCAGCCATCT GTAAACAATT TCAGTGGCAA CCCGCGAACT GTAATCCATG AATGGGACCA 120 CACTTTACAA GTCATCAAGT CTAACTTCTA GACCAGGGAA TTAATGGGGG AGACAGCGAA 180 CCCTAGAGCA AAGTGCCAAA CTTCTGTCGA TAGCTTGAGG CTAGTGGAAA GACCTCGAGG 240 AGGCTACTCC AGAAGTTCAG CGCGTAGGAA GCTCCGATAC CAATAGCCCT TTGATGATGG 300 TGGGGTTGGT GAAGGGAACA GTGCTCCGCA AGGTTATCCC TGCCCCAGGC AGTCCAATTT 360 TCACTCTGCA GATTCTCTCT GGCTCTAACT ACCCCAGATA ACAAGGAGTG AATGCAGAAT 420 AGCACGGGCT TTAGGGCCAA TCAGACATTA GTTAGAAAAA TTCCTACTAC ATGGTTTATG GGACCAGCTCACGCAC CTGTAGCTGAC CACTCCAAC 660 TGCGTCCGGA TCTTGGCTGG ATCGGACTCT CAGGGTGGAG GAGACACAAC CACAGCAGCT 720 GCCCftGCGTG TGCCCAGCCC TCCCACCGCT GGTCCCGGCT GCCAGGAGGC TGGCCGCTGG 780 CGGGAAGGGG CCGGGAAACC TCAGAGCCCC GCGGAGACAG CAGCCGCCTT GTTCCTCAGC 840 CCGGTGGCTT TTTTTTCCCC TGCTCTCCCA GGGGACAGAC ACCACCGCCC CACCCCTCAC 900 GCCCCACCTC CCTGGGGGAT CCTTTCCGCC CCAGCCCTGA AAGCGTTAAT CCTGGAGCTT 960 TCTGCACACC CCCCGACCGC TCCCGCCCAA GCTTCCTAAA AAAGAAAGGT GCAAAGTTTG 1020 GTCCAGGATA GAAAAATGAC TGATCAAAGG CAGGCGATAC TTCCTGTTGC CGGGACGCTA 1080 TATATAACGT GATGAGCGCA CGGGCTGCGG AGACGCACCG GAGCGCTCGC CCAGCCGCCG 1140 CCTCCAAGCC CCTGAGGTTT CCGGGGACCA CA ATG AAC AAG TTG CTG TGC TGC 1193 Met Asn Lys Leu Leu Leu Cys Cypress Cyg CGCCGGCGCCCGGGCGCCCGCGGGCGCCCG Leu Val GAGGCTGCTG CCACCTGGTC TCCCAACCTC CCAGCGGACC GGCGGGGAAA AAGGCTCCAC 1302 TCGCTCCCTC CCAAG 1317 This paper size applies to China National Standard (CNS) A4 specifications (210 X 297 mm) 123 38076 538 049 H3 GCTTACTTTG TGCCAAATCT CATTAGGCTT AAGGTAATAC AGGACTTTGA GTCAAATGAT 60 ACTGTTGCAC ATAAGAACAA ACCTATTTTC ATGCTA4GAT GATGCCACTG TGTTCCTTTC 120 TCCTTCTAG Thr ACC ACC ACC GACC ACACC -1 +1 CCT CCA AAG TAC CTT CAT TAT GAC GAA GAA ACC TCT CAT CAG CTG TTG 219 Pro Pro Lys Tyr Leu His Tyr Asp Glu Glu Thr Ser His Gin Leu Leu 5 10 15 TGT GAC AAA TGT CCT CCT GGT ACC TAC CTA AAA CAA CAC TGT ACA GCA 267 Cys Asp Lys Cys Pro Pro Gly Thr Tyr Leu Lys Gin His Cys Thr Ala 20 25 30 35 Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs This paper is in accordance with China National Standard (CNS) A4 specifications ( (210 X 297 mm) 124 38076 538049 H3 AAG TGG AAG ACC GTG TGC GCC CCT TGC CCT GAC CAC TftC TftC ACA GAC 315 Lys Trp Lys Thr Val Cys Ala Pro Cys Pro Asp His Tyr Tyr Thr Asp 40 45 50 AGC TGG CAC ACC AGT GAC GAG TGT CTA TAC TGC AGC CCC GTG TGC AAG 363 Ser Trp His Thr Ser Asp Glu Cys Leu Tyr Cys Ser Pro Val Cys Ly s 55 60 65 GAG CTG CAG TAC GTC AAG CAG GAG TGC AAT CGC ACC CAC AAC CGC GTG 411 Glu Leu Gin Tyr Val Lys Gin Glu Cys Asn Arg Thr His Asn Arg Val 70 75 80 TGC GAA TGC AAG GAA GGG CGC TAC CTT GAG ATA GAG TTC TGC TTG AAA 459 Cys Glu Cys Lys Glu Gly Arg Tyr Leu Glu lie Glu Phe Cys Leu Lys 85 90 95 CAT AGG ftGC TGC CCT CCT GCT TGA GTT GGA GTG GTG CAA GCT G GTACGTGTCA 509 His Arg Ser Cys Pro Pro Gly Phe Gly Val Val Gin Ala employee benefits Committee of economic Affairs Bureau of standards printed 100 105 110 ATGTGCAGCA AAATTAATTA GGATCATGCA AAGTCAGATA GTTGTGACAG under TTTAGGAGAA 569 CACTTTTGTT CTGATGACAT TATAGGATAG CAAATTGCAA AGGTAATGAA ACCTGCCAGG 629 TftGGTACTAT GTGTCTGGAG TGCTTCCAAA GGACCATTGC TCAGAGGAAT ACTTTGCCAC 689 TACAGGGCAA TTTAATGACA AATCTCAAAT GCAGCAflATT ATTCTCTCAT GAGATGCATG 749 ATGGTTTTTT TP Τ TAAAGAAACA AACTCAAGTT GCACTATTGA TAGTTGATCT 809 ATACCTCTAT ATTTCACTTC AGCATGGACA CCTTCAAACT GCAGCACTTT TTGACAAACA 869 TCAGAAATGT TAATTTATAC CAAGAGAGTA ATTATGCTCA TATTAATGAG ACTCTGGAGT 929 GCTAACA4TA AGCAGT TATA ATTAATTATG TAAAAAATGA GAATGGTGAG GGGAATTGCA 989 This paper size applies to the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 125 38076 538049 H3 Printed by the Staff Welfare Committee of the Central Bureau of Standards of the Ministry of Economic Affairs TTTCATTATT AAAAACAAGG CTAGTTCATCGCTTGGGACA 49 TATCTTAGAC AAAACAGATT 1109 GTCAAGCCAA GAGCAAGCAC TTGCCTATAA ACCAAGTGCT TTCTCTTTTG CATTTTGAAC 1169 AGCATTGGTC AGGGCTCATG TGTATTGAAT CTTTTAAACC AGTAACCCAC GTTTTTTTTC 1229 TGCCACATTT GCGAAGCTTC AGTGCAGCCT ATASCTTTTC ATAGCTTGAG AAAATTAAGA 1289 GTATCCACTT ACTTAGATGG AAGAAGTftAT CAGTATAGAT TCTGATGACT CAGTTTGAAG 1349 CAGTGTTTCT CAACTGAAGC CCTGCTGATA TTTTAAGAAA TATCTGGATT CCTAGGCTGG 1409 ACTCCTTTTT GTGGGCAGCT GTCCTGCGCA TTGTAGAATT TTGGCAGCAC CCCTGGACTC 1469 TAGCCACTAG ATACCAATAG CAGTCCTTCC CCCATGTGAC AGCCAAAAAT GTCTTCAGAC 1529 ACTGTCAAAT GTCGCCAGGT GGCAAAATCA CTCCTGGTTG AGAACAGGGT CATCAATGCT 1589 AAGTATCTGT AACTATTTTA ACTCTCAAAA CTTGTGATAT ACAAAGTCTS AATTATTAGA 1649 CGACCAATAC TTTAGGTTTA AAGGCATACA AATGAAACAT TCAAAAATCA AAATCTATTC 1709 TGTTTCTCAA ATflGTGAATC TTATAAAftTT AATCACAGAA GATGCAAATT GCATCAGAGT 1769 CCCTTAAAAT TCCTCTTCGT ATGAGTATTT GAGGGAGGAA TTGGTGATAG TTCCTACTTT 1829 CTATTGGATG GTACTTTGAG ACTCAAAAGC TAAGCTAAGT TGTGTGTGTG TCAGGGTGCG 1889 GGGTGTGGAA TCCCATCAGA TAAAAGCAAA TCCATGTAAT TCATTCAGTA AGTTGTATAT 1949 GTAGAAAAAT GAAAAGTGGG CTATGCAGCT TGGAAACTAG AGAATTTTGA AAAATAATGG 2009 AAATCACAAG G4TCTTTCTT AAATAAGTAA GAAAATCTGT TTGTAGAATG AAGCAAGCAG 2069 GCAGCCAGAA GACTCAGAAC AAAAGTACAC ATTTTACTCT GTGTACACTG GCAGCACAGT 2129 GGGATTTATT TACCTCTCCC TCCCTAAAAA CCCACACAGC GGTTCCTCTT GGGAAATAAG 2189 AGGTTTCCAG CCCAAAGAGA AGGAAAGACT ftTGTGGTGTT ACTCTAAAAA GTATTTAATA 2249 ACCGTTTTGT TGTT6CTGTT GCTGTTTTGA AATCAGATTG TCTCCTCTCC 4TATTTTATT 2309 TACTTCATTC TGTTAATTCC TGTGGSATTA CTTAGAGCAA GCATGGTGAA TTCTCAACTG 2369 TAAAGCCAAA TTTCTCCATC ATTATAATTT CACATTTTGC CTGGCAGGTT ATAATTTTTA 2429 TATTTCCACT GATAGTAATA AGGTAAAATC ATTACTTAGA TGGATAGATC TTTT TCATAA 2489 AAAGTACCAT CAGTTATAGA GGGAAGTCAT GTTCATGTTC AGGAAGGTCA TTAGATAAAG 2549 CTTCTGAATA TATTATGAAA CATTAGTTCT GTCATTCTTA GATTCTTTTT GTTAAATAAC 2609 TTTAAAAGCT AACTTACCTA AAAGAAATAT CTGACACATA TGAACTTCTC ATTAGGATGC 2669 Ben paper scale applicable to Chinese National Standard (CNS) A4 size (210 Father 297 Kimiyoshi) 126 38076 538049 H3 Ministry of Economic Affairs Central Standard Bureau of employee benefits Committee printed AGGAGAAGAC CCAAGCCACA GATATGTATC TGAAGAATGA ACAAGATTCT TAGGCCCGGC 2729 ACGGTGGCTC ACATCTGTAA TCTCAAGAGT TTGAGAGGTC AAGGCGGGCA GATCACCTGA 2789 GGTCAGGAGT TCAAGACCAG CCTGGCCAAC ATGATGAAAC CCTGCCTCTA CTAAAAATAC 2849 AAAAATTAGC AGGGCATGGT GGTGCATGCC TGCAACCCTA GCTACTCAGG AGGCTGAGAC 2909 AGGAGAATCT CTTGAACCCT CGAGGCGGAG GTTGTGGTGA GCTGAGATCC CTCTACTGCA 2969 CTCCAGCCTG GGTGACAGAG ATGAGACTCC GTCCCTGCCG CCGCCCCCGC CTTCCCCCCC 3029 AAAAAGATTC TTCTTCATGC ftGAACATACG GCAGTCAACA AAGGGAGACC TGGGTCCAGG 3089 TGTCCAAGTC ACTTATTTCG AGTAAATTAG CAATGAAAGA ATGCCATGGA ATCCCTGCCC 3149 AAATACCTCT GCTTATGATA TTGTAGAATT TGATAT AGAG TTGT4TCCCA TTTAAGGAGT 3209 AGGATGTAGT AGGAAAGTAC TAAAAACAAA CACACAAACA GAAAACCCTC TTTGCTTTGT 3269 AAGGTGGTTC CTAAGATAAT GTCAGTGCAA TGCTGGAAAT AATATTTAAT ATGTGAAGGT 3329 TTTAGGCTGT GTTTTCCCCT CCTGTTCTTT TTTTCTGCCA GCCCT1TGTC ATTTTTGCAG 3389 GTCAATGAAT CATGTAGAAA GAGACAGGAG ATGAAACTAG AACCAGTCCA TTTTGCCCCT 3449 TTTTTTATTT TCTGGTTTTG GTftAAAGATA CAATGAGGTA GGAGGTTGAG ATTTATAAAT 3509 GAAGTTTAAT AAGTTTCTGT AGCTTTGATT TTTCTCTTTC ATATTTGTTA TCTTGCATAA 3569 GCCAGAATTG GCCTGTAAAA TCTACATATG GATATTGAAG TCTAAATCTG TTCAACTAGC 3629 TTACACTAGA TGGAGATATT TTCATATTCA GATACACTGG AATGTATGAT CTAGCCATGC 3689 GTAATATAGT CAAGTGTTTG AAGGTATTTA TTTTTAATAG CGTCTTTAGT TGTGGACTGG 3749 TTCAAGTTTT TCTGCCAATG ATTTCTTCAA 4TTTATCAAA TATTTTTCCA TCATGAAGTA 3809 AAATGCCCTT GCAGTCACCC TTCCTGAAGT TTGAACGACT CTGCTGTTTT AAACAGTTTA 3869 AGCAAATGGT ATATCATCTT CCGTTTACTA TGTAGCTTAA CTGCAGGCTT ACGCTTTTGA 3929 GTCAGCGGCC AACTTTATTG CCACCTTCAA AAGTTTATTA TAATGTTGTA AATTTTTACT 3989 TCTCAAGGTT AGCATACTTA GGAGTTGC TT CACAATTAGG ATTCAGGAAA GAAAGAACTT 4049 CAGTAGGAAC TGATTGGAAT TTAATGATGC AGCATTCAAT GGGTACTAAT TTCAAAGAAT 4109 GATATTACAG CAGACACACA GCAGTTATCT TGATTTTCTA GGAATAATTG TATGAAGAAT 4169 ATGGCTGACA ACACGGCCTT ACTGCCACTC AGCGGAGGCT GGftCTAATGA ACACCCTACC 4229 CTTCTTTCCT TTCCTCTCAC ATTTCATGAG CGTTTTGTAG GTAACGAGAA AATTGACTTG 4289 CATTTGCATT ACAAGGAGGA GAAACTGGCA AAGGGGATGA TGGTGGAAGT TTTGTTCTGT 4349 Ben paper scale applicable to Chinese National Standard (CNS) A4 specifications (210 X 297 mm) 127 38076 538049 H3 Printed by the Employee Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs CTAATGAAGT GAAAAATGftA AATGCTAGAG TTTTGTGCAA CATAATAGTA GCAGTAAAAA 4409 CCAAGTGAAA AGTCTTTCCA AAACTGCA ATGATTGAG TA469 4 Thr Pro Glu Arg Asn Thr 115 GTT TGC AAA AGA TGT CCA GAT GGG TTC TTC TCA AAT GAG ACG TCA TCT 4571 Val Cys Lys Arg Cys Pro Asp Gly Phe Phe Ser Asn Glu Thr Ser Ser 120 125 130 135 AAA GCA CCC TGT AGA AAA CAC ACA AAT TGC AGT GTC TTT GGT CTC CTG 4619 Lys Ala Pro Cys Arg Lys His Thr Asn Cys Ser Val Phe Gly Leu Leu 140 145 150 CTA ACT CAG AAA GGA AAT GCA ACA CAC GAC AAC ATA TGT TCC GGA AAC 4667 Lea Thr Gin Lys Gly Asn Ala Thr His Asp Asn lie Cys Ser Gly Asn 155 160 165 AGT GAA TCA ACT CAA AAA TGT GGA ATA G GTAATTACAT TCCAAAATAC 4715 Ser Glu Ser Thr Gin Lys Cys Gly lie 170 175 GTCTTTGTAC GATTTTGTCCACTAGCTCAGCGCAGC TACCACTCAG AATCTCTCAA AAACTCATCT TCTCACAGAT 4895 AACACCTCAA AGCTTGATTT TCTCTCCTTT CACACTGAAA TCAAATCTTG CCCATAGGCA 4955 AAGGGCAGTG TCAAGTTTGC CACTGAGATG AAATTAGGAG AGTCCAAACT GTAGAATTCA 5015 CGTTGTGTGT TATTACTTTC ACGAATGTCT GTATTATTAA CTAAAGTATA TATTGGCAAC 5075 Ben paper scale applicable to Chinese national standard (CNS) A4 size (210 X 297 Kimiyoshi) 128 38076 538049 H3 economy Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of TAAGAAGCAA AGTGATATAA ACATGATGAC AAATTAGGCC AGGCATGGTG GCTTACTCCT 5135 ATAATCCCAA CATTTTGGGG GGCCAAGGTA GGCAGATCAC TTGAGGTCAG GATTTCAAGA 5195 CCAGCCTGAC CAACATGGTG AAACCTTGTC TCTACTAAAA ATACAAAAAT TAGCTGGGCA 5255 TGGTAGCAGG CACTTCTAGT ACCAGCTACT CAGGGCTGAG GCAGGAGAAT CGCTTGAACC 5315 CAGGAGATGG AGGTTGCAGT GAGCTGAGAT TGT4CCACTG CACTCCAGTC TGGGCAACAG 5375 AGCAAGATTT CATCACACAC ACACACACAC ACACACACAC ACACATTAGA AATGTGTftCT 5435 TGGCTTTGTT ACCTATGGTA TTAGTGCATC TATTGCATGG AACTTCCAAG CTACTCTGGT 5495 TGTGTTAAGC TCTTCATTGG GTACAGGTCA CTAGTATTAA GTTCAGGTTA TTCGGATGCA 5555 TTCCACGGTA GTGATGACAA TTCATC4GGC TAGTGTGTGT GTTCACCTTG TCACTCCCAC 5615 CACTAGACTA ATCTCAGACC TTCACTCAAA GACACATT4C ACTAAAGATG ATTTGCTTTT 5675 TTGTGTTTAA TCAAGCAATG GTATAAACCA GCTTGACTCT GCCCAAACAG TTTTTCGTAC 5735 TACAAAGAAG TTTATGAAGC AGAGAAATGT GAATTGATAT ATATATGAGA TTCTAACCCA 5795 GTTCCAGCAT TGTTTCATTG TGTAATTGAA ATCATAGACA AGCCATTTTA GCCTTTGCTT 5855 TCTTATCTAA AAAAAAAAAA AAAAAAATGA AGGAAGGGGT 4TTAAAAGGA GTGATCAAAT 5915 TTTAACATTC TCTTTAATTA ATTCATTTTT AATTTTACTT TTTTTCATTT AT TGTGCACT 5975 T4CTATGTGG TACTGTGCTA TAGAGGCTTT AACATTTATA AAAACACTGT GAAAGTTGCT 6035 TCAGATGAAT ATAGGTAGTA GAACGGCAGA ACTAGTATTC AAAGCCAGGT CTGATGAATC 6095 CAAAAACAAA CACCCATTAC TCCCATTTTC TGGGACATAC TTACTCTACC CAGATGCTCT 6155 GGGCTTTGTA ATGCCTATGT AAATAACATA GTTTTATGTT TGGTTATTTT CCTATGTAAT 6215 GTCTACTTAT ATATCTGTAT CTATCTCTTG CTTTGTTTCC AAAGGTAAAC TATGTGTCTA 6275 AATGTGGGCA AAAAATAACA CACTATTCCA AATTACTGTT CAAATTCCTT TAAGTCAGTG 6335 ATAATTATTT GTTTTGACAT TAATCATGAA GTTCCCTGTG GGTACTAGGT AAACCTTTAA 6395 TAGAATGTTA ATGTTTGTAT TCATTATAAG AATTTTTGGC TGTTACTTAT TTACAACAAT 6455 ATTTCACTCT AATTAGACAT TTACTAAACT TTCTCTTGAA AACAATGCCC AAAAAAGAAC 6515 ATTAGAAGAC ACGTAAGCTC SGTTGGTCTC TGCCACTAAG ACCAGCCAAC AGAAGCTTGA 6575 TTTTATTCAA ACTTTGCATT TTAGCATATT TTATCTTGGA AAATTCAATT GTGTTGGTTT 6635 TTTGTTTTTG TTTGTATTGA ATAGACTCTC AGAAATCCAA TTGTTGAGTA AflTCTTCTGG 6695 GTTTTCTAAC CTTTCTTTAG AT GTT ACC CTG TGT GAG GAG GCA TTC TTC AGG 6747 This paper size applies to Chinese National Standard (CNS) A4 Specifications (210 X 297 mm) 129 38076 538049 H3 Asp Val Thr Leu Cys Gla Glu Ala Phe Phe Arg 180 185 TTT GCT GTT CCT ACA AAG TTT ACG CCT AAC TGG CTT AGT GTC TTG GTA 6795 Phe Ala Vai Pro Thr Lys Phe Thr Pro Asm Trp Leu Ser Val Leu Val 190 195 200 GAC AAT TTG CCT GGC ACC AAA GTA AAC GCA GAG AGT GTA GAG AGG ftTA 6843 Asp Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg lie 205 210 215 AAA CGG CAA CAC AGC TCA CAA GAA CAG ACT TTC CAG CTG CTG AAG TTA 6891 Lys Arg Gin His Ser Ser Gin Glu Gin Thr Phe Gin Leu Leu Lys Leu 220 225 230 235 TGG AAA CAT CAA AAC AAA GAC CAA GAT ATA GTC AAG AAG 4TC ATC CAA G 6940 Trp Lys His Gin Asn Lys Asp Gin Asp lie Val Lys Lys lie lie Gin 240 245 250 GTAATTACAT TCCAAAATAC GTCTTTGTAC GATTTTGTAG TATCATCTCT CTCTCTGAGT 7000 TGAACACAAG GCCTCCAGCC ACATTCTTGG TCAAACTTAC ATTTTCCCTT TCTTGAATCT 7060 TAACCAGCTA AGGCTACTCT CGATGCATTA CTGCTAAAGC TACCACTCAG AATCTCTCAA 7120 AAACTCATCT TCTCACAGAT AACACCTCAA AGCTTGATTT TCTCTCCTTT CACACTGAftA 7180 TCAAAT CTTG CCCATAGGCA AAGGGCAGTG TCAAGTTTGC CACTGAGATG AAATTAGGAG Employee Benefits Committee of Economic Affairs Bureau of Standards 7240 printed AGTCCAAACT GTAGAATTCA CGTTGTGTGT TATTACTTTC ACGAATGTCT GTATTATTAA 7300 CTAAAGTATA TATTGGCAAC TAAGAAGCAA AGTGATATAA ACATGATGAC AAATTAGGCC 7360 AGGCATGGTG GCTTACTCCT ATAATCCCAA CATTTTGGGG GGCCAAGGTA GGCAGATCAC 7420 TTGAGGTCAG GATTTCAAGA CCAGCCTGAC CAACATGGTG AAACCTTGTC TCTACTAAAA 7480 Ben paper scale applicable to China national standards (CNS) A4 size (210 X 297 mm) 130 38076 538049 H3 ATACAAAAAT TAGCTGGGCA TGGTAGCAGG CACTTCTAGT ACCAGCTACT CAGGGCTGAG 7540 GCAGGAGAAT CGCTTGAACC CAGGAGATGG AGGTTGCAGT GAGCTGAGAT TGTACCACTG 7600 CACTCCAGTC TGGGCAACAG AGCAAGATTT CATCACACAC ACACACACAC ACACACACAC 7660 ACACATTAGA AATGTGTACT TGGCTTTGTT ACCTATGGTA TTAGTGCATC TATTGCATGG 7720 AACTTCCAAG CTACTCTGGT TGTGTTAAGC TCTTCATTGG GTACAGGTCA CTAGTATTAA 7780 GTTCAGGTTA TTCGGATGCA TTCCACGGTA GTGATGACAA TTCATCAGGC TAGTGTGTGT 7840 GTTCACCTTG TCACTCCCAC CACTAGACTA ATCTCAGACC TTCACTCAAA GACA CATTAC 7900 ACTAAAGATG ATTTGCTTTT TTGTGTTTAA TCAAGCAATG GTATAftACCA GCTTGACTCT 7960 CCCCAAACAG TTTTTCGTAC TACAAAGAAG TTTATGAAGC AGAGAAATGT GAATTGATAT 8020 ATATATGAGA TTCTAACCCA GTTCCAGCAT TGTTTCATTG TGTAATTGAA ATCATAGACA 8080 AGCCATTTTA GCCTTTGCTT TCTTATCTAA AAAAAAAAAA AAAAAAATGA AGGAAGGGGT 8140 ATTAAAAGGA GTGATCAAAT TTTAACATTC TCTTTAATTA ATTCATTTTT AATTTTACTT 8200 TTTTTCATTT ATTGTGCACT TACTATGTGG TACTGTGCTA TAGAGGCTTT AACATTTATA 8260 AAAACACTGT GAAAGTTGCT TCAGATGAAT ATAGGTAGTA GAACGGCAGA ACTAGTATTC 8320 AAAGCCAGGT CTGATGAATC CAAAAACAAA CACCC4TTAC TCCCATTTTC TGGGACATAC 8380 TTACTCTACC CAGATGCTCT GGGCTTTGTA ATGCCTATGT AAATAACATA GTTTTATGTT 8440 TGGTTATTTT CCTATGTAAT GTCTACTTAT ATATCTGTAT CTATCTCTTG CTTTGTTTCC 8500 AAAGGTAAAC T4TGTGTCTA AATGTGGGCA AAAAATAACA CACTATTCCA AATTACTGTT 8560 CAAATTCCTT TAAGTCAGTG ATAATTATTT GTTTTGACAT TAATCATGAA GTTCCCTGTG 8620 GGTACTAGGT AAACCTTTAA TAGAATGTTA ATGTTTGTAT TCATTATAAG AATTTTTGGC 8680 TGTTACTTAT TTACAACAAT ATTTCACTCT AATTAGACAT TTACTA AACT TTCTCTTGAA 8740 AACAATGCCC AAAAAAGAAC ATTAGAAGAC ACGTAAGCTC AGTTGGTCTC TGCCSCTAAG 8800 ACCAGCCAAC AGA4GCTTGA TTTTATTCAA ACTTTGCATT TTAGCATATT TTATCTTGGA 8860 AAATTCAATT GTGTTGGTTT TTTGTTTTTG TTTGTATTGA ATAGACTCTC AGAAATCCAA 8920 TTGTTGAGTA AATCTTCTGG GTTTTCTAAC CTTTCTTTAG AT ftTT GAC CTC TGT 8974 Asp lie Asp Leu Cys Employee Benefits Committee of Economic Affairs Bureau of Standards printed 255 This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 131 38076 538049 H3 Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs GAA AAC AGC GTG CAG CGG CAC ATT GGA CAT GCT AAC CTC ACC TTC GAG 9022 GIu Asn Ser Val Gin Arg His lie Gly His Ala Asn Leu Thr Phe Glu 260 265 270 CAG CTT CGT AGC TTG ATG GAA AGC TTA CCG GGA AAG AAA GTG GGA GCA 9070 Gin Leu Arg Ser Leu Met GIu Ser Leu Pro Gly Lys Vals Gly Ala 275 280 285 GAA GAC ATT GAA AAA ACA ATA AAG GCA TGC AAA CCC AGT GAC CAG ATC 9118 Glu Asp lie Glu Lys Thr lie Lys Ala Cys Lys Pro Ser Asp Gin lie 290 295 300 'CTG MG CTG CTC AGT TT G TGG CGA ATA AAA AAT GGC GAC CAA GAC ACC 9166 Leu Lys Leu Lea Ser Leu Trp Arg lie Lys Asn Gly Asp Gin Asp Thr 305 310 315 320 TTG AAG GGC CTA ATG CAC GCA CTA AAG CAC TCA AAG ACG TAC CAC TTT 9214 Leu Lys Gly Leu Met His Ala Leu Lys His Ser Lys Thr Tyr His Phe 325 330 335 CCC AAA ACT GTC ACT CAG AGT CTA AAG AAG ACC ATC AGG TTC CTT CAC 9262 Pro Lys Thr Val Thr Gin Ser Leu Lys Lys Thr He Arg Phe Leu His 340 345 350 AGC TTC ACA ATG TAC AAA TTG TAT CAG AAG TTA TTT TTA GAA ΛΤ6 ATA 9310 Ser Phe Thr Met Tyr Lys Leu Tyr Gin Lys Leu Phe Leu Glu Met lie 355 360 365 This paper is compatible with the Chinese National Standard (CNS) A4 size (210 X 297 mm) 132 38076 538049 Printed by the Employee Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs H3 _ GGT AAC CAG GTC CAA TCA GTA AAA ATA AGC TGC TTA TAACTGGAAA 9356 Giy Asn Gin Val Gin Ser Val Lys lie Ser Cys Leu 370 375 380 TGGCCATTGA GCTGTTTCCT CACAATTGGC GAGATCCCAT GGATGAGTAA ACTGTTTCTC 9416 AGGCACTTGA GGCTTTCAGT GATATCTTTC TCATTACCAG TGACTAATTT TGCCACAGGG 9476 TACTAAAAGA AAC TATGATG TGGAGAAAGG ACTAACATCT CCTCCAATAA ACCCCAAATG 9536 GTTAATCCAA CTGTCAGATC TGGATCGTTA TCTACTGACT ATATTTTCCC TTATTACTGC 9596 TTGCftGTAAT TCAACTGGAA ATTAAAAAAA AAAAACTAGA CTCCACTGGG CCTTACTAAA 9656 TATGGGAATG TCTAACTTAA ATAGCTTTGG GATTCCAGCT ATGCTAGAGG CTTTTATTAG 9716 AAAG'CCATAT TTTTTTCTGT AAAAGTTACT AATATATCTG TAACACTATT ACAGTATTGC 9776 TATTTATATT CATTCAGATA TAAGATTTGG ACATATTATC ATCCTATAAA GAAACGGTAT 9836 GACTTAATTT TAGAAAGAAA ATTATATTCT GTTTATTATG ACAAATGAAA GAGAAAATAT 9896 ATATTTTTAA TGGAAAGTTT GTAGCATTTT TCTAATAGGT ACTGCCATAT TTTTCTGTGT 9956 GGAGTATTTT TATAATTTTA TCTGTATAAG CTGTAATATC ATTTTATAGA AAATGCATTA 10016 TTTAGTCAAT TGTTTAATGT TGGAAAACAT ATGAAATATA AATTATCTGA ATATTAGATG 10076 CTCTGAGAAA TTGAATGTAC CTTATTTAAA AGATTTTATG GTTTTATAAC TATATAAATG 10136 ACATTATTAA AGTTTTCAAA TTATTTTTTA TTGCTTTCTC TGTTGCTTTT ATTT 10190 o 8 8. - kinds of therapeutic agents for osteoporosis, to apply lines The first or fourth item of the patent covers proteins that inhibit human osteoclast formation as effective ingredients. 8 9. —A therapeutic agent for osteopenia, which uses the protein that inhibits the formation of human osteoclasts as the active ingredient in the scope of patent application No. 1 or 4. 90. An agent for treating abnormal bone metabolism, which uses as an active ingredient a protein that inhibits the formation of human osteoclasts in the scope of patent application No. 1 or 4. 91. A specific affinity polyclonal antibody, which is a polyclonal antibody having specific affinity for a protein that inhibits the formation of human osteoclasts in the scope of claims 1 or 4. 92. A method for measuring a human osteoclast formation inhibitory factor, characterized in that it is measured using a plurality of strains of antibodies of the scope of application for patent 91. This paper size applies to China National Standard (CNS) A4 (210 x 297 mm) 133 38076